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Studying the Function of RNAs Using Omics Approaches

A special issue of Current Issues in Molecular Biology (ISSN 1467-3045). This special issue belongs to the section "Biochemistry, Molecular and Cellular Biology".

Deadline for manuscript submissions: closed (31 July 2023) | Viewed by 25197

Special Issue Editors

Department of Biochemistry and Biophysics, University of Rochester, 601 Elmwood Ave, Rochester, NY 14642, USA
Interests: small RNA; bioinformatics
Department of Psychiatry, University of Texas Southwestern Medical Center, Dallas, TX, USA
Interests: iPSC/ES cell culture; neural cell differentiation/culture; RNA sequencing/analyses; schizophrenia

Special Issue Information

Dear Colleagues,

RNA is critical to life, passing the information from genomic DNA to the downstream life processes, for example, translation and RNA-mediated gene regulation. RNAs are also diverse, including messenger RNA, small non-coding RNA, circular RNA, etc. Studying the function of RNA molecules has been a central topic in molecular biology. In this Special Issue, we focus on the mechanisms of RNA regulations in cells, including both in vivo and in vitro studies of RNA molecules. We look forward to a wide variety of omics approaches to study RNAs and dissect RNA processing and regulation steps. We anticipate high-throughput studies using next-generation sequencing to power the investigation of RNAs at the transcriptome scale, such as RNA-seq, single-cell RNA-seq, third-generation sequencing of RNAs, etc. In addition to mRNAs, studies focusing on other types of RNAs, such as non-coding RNAs and small RNAs, are also welcome. We aim to collect cutting-edge studies covering fundamental topics of the current RNA research. This Special Issue also encourages collaborative and interdisciplinary projects that span more than one field.

Dr. Yu Sun
Dr. Zhengshan Liu
Guest Editors

Manuscript Submission Information

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Keywords

  • next-generation sequencing
  • RNA modification
  • small RNA
  • single-cell RNA-seq
  • bioinformatics

Published Papers (17 papers)

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18 pages, 7464 KiB  
Article
In Silico Bioinformatics Analysis on the Role of Long Non-Coding RNAs as Drivers and Gatekeepers of Androgen-Independent Prostate Cancer Using LNCaP and PC-3 Cells
by Mandisa Mbeje, Jeyalakshmi Kandhavelu, Clement Penny, Mmamoletla Kgoebane-Maseko, Zodwa Dlamini and Rahaba Marima
Curr. Issues Mol. Biol. 2023, 45(9), 7257-7274; https://doi.org/10.3390/cimb45090459 - 01 Sep 2023
Viewed by 1184
Abstract
Prostate cancer (PCa) is the leading cancer in men globally. The association between PCa and long non-coding RNAs (lncRNAs) has been reported. Aberrantly expressed lncRNAs have been documented in each of the cancer “hallmarks”. Androgen signaling plays an important role in PCa progression. [...] Read more.
Prostate cancer (PCa) is the leading cancer in men globally. The association between PCa and long non-coding RNAs (lncRNAs) has been reported. Aberrantly expressed lncRNAs have been documented in each of the cancer “hallmarks”. Androgen signaling plays an important role in PCa progression. This study aimed to profile the aberrantly expressed lncRNAs in androgen-dependent (LNCaP) PCa compared to androgen-independent (PC-3) PCa cells. This was achieved by using a 384-well plate of PCa lncRNA gene panel. Differential expression of ±2 up or downregulation was determined using the CFX Maestro software v2.1. LncSEA and DIANA-miRPath were used to identify the enriched pathways. Telomerase RNA component (TERC) lncRNA was illustrated to participate in various tumourigenic classes by in silico bioinformatics analysis and was thus selected for validation using RT-qPCR. Further bioinformatics analysis revealed the involvement of differentially expressed lncRNAs in oncogenic pathways. Some lncRNAs undergo hypermethylation, others are encapsulated by exosomes, while others interact with several microRNAs (miRNAs), favouring tumourigenic pathways. Notably, TERC lncRNA was shown to interact with tumour-suppressor miRNAs hsa-miR-4429 and hsa-miR-320b. This interaction in turn activates TGF-β-signaling and ECM-receptor interaction pathways, favouring the progression of PCa. Understanding lncRNAs as competitive endogenous RNA molecules and their interactions with miRNAs may aid in the identification of novel prognostic PCa biomarkers and therapeutic targets. Full article
(This article belongs to the Special Issue Studying the Function of RNAs Using Omics Approaches)
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12 pages, 2162 KiB  
Article
Long Noncoding RNA TALAM1 Is a Transcriptional Target of the RUNX2 Transcription Factor in Lung Adenocarcinoma
by Gisella Bermúdez, Camila Bernal, Andrea Otalora, Paula Sanchez, Gino Nardocci, Alejandra Cañas, Liliana Lopez-Kleine, Martín Montecino and Adriana Rojas
Curr. Issues Mol. Biol. 2023, 45(9), 7075-7086; https://doi.org/10.3390/cimb45090447 - 24 Aug 2023
Viewed by 1442
Abstract
Background: Lung cancer is the leading cause of cancer death worldwide. It has been reported that genetic and epigenetic factors play a crucial role in the onset and evolution of lung cancer. Previous reports have shown that essential transcription factors in embryonic development [...] Read more.
Background: Lung cancer is the leading cause of cancer death worldwide. It has been reported that genetic and epigenetic factors play a crucial role in the onset and evolution of lung cancer. Previous reports have shown that essential transcription factors in embryonic development contribute to this pathology. Runt-related transcription factor (RUNX) proteins belong to a family of master regulators of embryonic developmental programs. Specifically, RUNX2 is the master transcription factor (TF) of osteoblastic differentiation, and it can be involved in pathological conditions such as prostate, thyroid, and lung cancer by regulating apoptosis and mesenchymal–epithelial transition processes. In this paper, we identified TALAM1 (Metastasis Associated Lung Adenocarcinoma Transcript 1) as a genetic target of the RUNX2 TF in lung cancer and then performed functional validation of the main findings. Methods: We performed ChIP-seq analysis of tumor samples from a patient diagnosed with lung adenocarcinoma to evaluate the target genes of the RUNX2 TF. In addition, we performed shRNA-mediated knockdown of RUNX2 in this lung adenocarcinoma cell line to confirm the regulatory role of RUNX2 in TALAM1 expression. Results: We observed RUNX2 overexpression in cell lines and primary cultured lung cancer cells. Interestingly, we found that lncRNA TALAM1 was a target of RUNX2 and that RUNX2 exerted a negative regulatory effect on TALAM1 transcription. Full article
(This article belongs to the Special Issue Studying the Function of RNAs Using Omics Approaches)
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19 pages, 5036 KiB  
Article
Identifying circRNA–miRNA–mRNA Regulatory Networks in Chemotherapy-Induced Peripheral Neuropathy
by Fei Cao, Xintong Wang, Qingqing Ye, Fang Yan, Weicheng Lu, Jingdun Xie, Bingtian Bi and Xudong Wang
Curr. Issues Mol. Biol. 2023, 45(8), 6804-6822; https://doi.org/10.3390/cimb45080430 - 16 Aug 2023
Viewed by 1186
Abstract
Chemotherapy-induced peripheral neuropathy (CIPN) is a frequent and severe side effect of first-line chemotherapeutic agents. The association between circular RNAs (circRNAs) and CIPN remains unclear. In this study, CIPN models were constructed with Taxol, while 134 differentially expressed circRNAs, 353 differentially expressed long [...] Read more.
Chemotherapy-induced peripheral neuropathy (CIPN) is a frequent and severe side effect of first-line chemotherapeutic agents. The association between circular RNAs (circRNAs) and CIPN remains unclear. In this study, CIPN models were constructed with Taxol, while 134 differentially expressed circRNAs, 353 differentially expressed long non-coding RNAs, and 86 differentially expressed messenger RNAs (mRNAs) were identified utilizing RNA sequencing. CircRNA-targeted microRNAs (miRNAs) were predicted using miRanda, and miRNA-targeted mRNAs were predicted using TargetScan and miRDB. The intersection of sequencing and mRNA prediction results was selected to establish the circRNA–miRNA–mRNA networks, which include 15 circRNAs, 18 miRNAs, and 11 mRNAs. Functional enrichment pathway analyses and immune infiltration analyses revealed that differentially expressed mRNAs were enriched in the immune system, especially in T cells, monocytes, and macrophages. Cdh1, Satb2, Fas, P2ry2, and Zfhx2 were further identified as hub genes and validated by RT-qPCR, correlating with macrophages, plasmacytoid dendritic cells, and central memory CD4 T cells in CIPN. Additionally, we predicted the associated diseases, 36 potential transcription factors (TFs), and 30 putative drugs for hub genes using the DisGeNET, TRRUST, and DGIdb databases, respectively. Our results indicated the crucial role of circRNAs, and the immune microenvironment played in CIPN, providing novel insights for further research. Full article
(This article belongs to the Special Issue Studying the Function of RNAs Using Omics Approaches)
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12 pages, 1277 KiB  
Article
An mRNA Profiling Study of Vaginal Swabs from Pre- and Postmenopausal Women
by Elena Chierto, Federica Alessandrini, Carla Bini, Eugenia Carnevali, Matteo Fabbri, Paolo Fattorini, Pierangela Grignani, Francesca Scarnicci, Pamela Tozzo, Andrea Verzeletti, Susi Pelotti, Loredana Buscemi and Carlo Robino
Curr. Issues Mol. Biol. 2023, 45(8), 6526-6537; https://doi.org/10.3390/cimb45080411 - 07 Aug 2023
Viewed by 951
Abstract
Body fluid identification by means of mRNA profiling provides valuable supplementary information in forensic investigations. In particular, the detection of vaginal mucosa mRNA markers is highly relevant in sexual assault cases. Although the vagina undergoes characteristic age-related physiological changes over a lifetime, few [...] Read more.
Body fluid identification by means of mRNA profiling provides valuable supplementary information in forensic investigations. In particular, the detection of vaginal mucosa mRNA markers is highly relevant in sexual assault cases. Although the vagina undergoes characteristic age-related physiological changes over a lifetime, few studies have evaluated the efficacy of vaginal mRNA markers in women of different ages. In this multicentric study, a 19-plex mRNA profiling assay including vaginal-specific markers (CYP2B7P1, MUC4, MYOZ1) was tested in a collection of 6–20-month-old vaginal swabs obtained from pre- (n = 84) and postmenopausal (n = 55) female volunteer donors. Overall, participating laboratories were able to correctly identify ~85% of samples as vaginal mucosa by mRNA profiling. The assay’s success rate did not differ between the two age groups and was not affected by the time interval between swab collection and RNA analysis. MYOZ1 resulted a less sensitive vaginal marker compared to MUC4 and CYP2B7P1. A significant relative increase in the contribution to the total amplification signal was observed for MUC4, compared to CYP2B7P1 and MYOZ1, in postmenopausal women. Observation of other body fluids and tissues different from vaginal mucosa was also evaluated in connection to information on previous sexual activity and menstrual cycle phase at the time of sampling. Full article
(This article belongs to the Special Issue Studying the Function of RNAs Using Omics Approaches)
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20 pages, 7378 KiB  
Article
Insight into the lncRNA–mRNA Co-Expression Profile and ceRNA Network in Lipopolysaccharide-Induced Acute Lung Injury
by Yue Shen, Linjing Gong, Fan Xu, Sijiao Wang, Hanhan Liu, Yali Wang, Lijuan Hu and Lei Zhu
Curr. Issues Mol. Biol. 2023, 45(7), 6170-6189; https://doi.org/10.3390/cimb45070389 - 24 Jul 2023
Viewed by 1083
Abstract
Long non-coding RNAs (lncRNAs) participate in acute lung injury (ALI). However, their latent biological function and molecular mechanism have not been fully understood. In the present study, the global expression profiles of lncRNAs and mRNAs between the control and lipopolysaccharide (LPS)-stimulated groups of [...] Read more.
Long non-coding RNAs (lncRNAs) participate in acute lung injury (ALI). However, their latent biological function and molecular mechanism have not been fully understood. In the present study, the global expression profiles of lncRNAs and mRNAs between the control and lipopolysaccharide (LPS)-stimulated groups of human normal lung epithelial cells (BEAS-2B) were determined using high-throughput sequencing. Overall, a total of 433 lncRNAs and 183 mRNAs were differentially expressed. A lncRNA–mRNA co-expression network was established, and then the top 10 lncRNAs were screened using topological methods. Gene Ontology and Kyoto Encyclopedia of Genes and Genomes analysis results showed that the key lncRNAs targeting mRNAs were mostly enriched in the inflammatory-related biological processes. Gene set variation analysis and Pearson’s correlation coefficients confirmed the close correlation for the top 10 lncRNAs with inflammatory responses. A protein–protein interaction network analysis was conducted based on the key lncRNAs targeting mRNAs, where IL-1β, IL-6, and CXCL8 were regarded as the hub genes. A competing endogenous RNA (ceRNA) modulatory network was created with five lncRNAs, thirteen microRNAs, and twelve mRNAs. Finally, real-time quantitative reverse transcription-polymerase chain reaction was employed to verify the expression levels of several key lncRNAs in BEAS-2B cells and human serum samples. Full article
(This article belongs to the Special Issue Studying the Function of RNAs Using Omics Approaches)
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14 pages, 11567 KiB  
Article
Interactions of piRNAs with the mRNA of Candidate Genes in Esophageal Squamous Cell Carcinoma
by Aizhan Rakhmetullina, Aigul Akimniyazova, Togzhan Niyazova, Anna Pyrkova, Makpal Tauassarova, Anatoliy Ivashchenko and Piotr Zielenkiewicz
Curr. Issues Mol. Biol. 2023, 45(7), 6140-6153; https://doi.org/10.3390/cimb45070387 - 23 Jul 2023
Viewed by 1253
Abstract
Recently, a database of human piRNAs (piwi-interacting RNAs) was created, which allows the study of the binding of many piRNAs to the mRNAs of genes involved in many diseases, including cancer. In the present work, we identified the piRNAs that can interact with [...] Read more.
Recently, a database of human piRNAs (piwi-interacting RNAs) was created, which allows the study of the binding of many piRNAs to the mRNAs of genes involved in many diseases, including cancer. In the present work, we identified the piRNAs that can interact with candidate esophageal squamous cell carcinoma (ESCC) genes. The binding of 480 thousand piRNAs with the mRNAs of 66 candidate ESCC genes was studied. Bioinformatic studies found that piRNAs bind only to the mRNAs of nine candidate genes: AURKA, BMP7, GCOM1, ERCC1, MTHFR, SASH1, SIX4, SULT1A1, and TP53. It has been shown that piRNAs can bind to mRNA by overlapping nucleotide sequences in limited 3′UTR and 5′UTR regions called clusters of binding sites (BSs). The existence of clusters of piRNA BSs significantly reduces the proportion of the nucleotide sequences of these sites in the mRNA of target genes. Competition between piRNAs occurs for binding to the mRNA of target genes. Individual piRNAs and groups of piRNAs that have separate BSs and clusters of BSs in the mRNAs of two or more candidate genes have been identified in the mRNAs of these genes. This organization of piRNAs BSs indicates the interdependence of the expression of candidate genes through piRNAs. Significant differences in the ability of genes to interact with piRNAs prevent the side effects of piRNAs on genes with a lack of the ability to bind such piRNAs. Individual piRNAs and sets of piRNAs are proposed and recommended for the diagnosis and therapy of ESCC. Full article
(This article belongs to the Special Issue Studying the Function of RNAs Using Omics Approaches)
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18 pages, 5143 KiB  
Article
A Prochlorperazine-Induced Decrease in Autonomous Muscle Activity during Hindlimb Unloading Is Accompanied by Preserved Slow Myosin mRNA Expression
by Kristina A. Sharlo, Irina D. Lvova, Sergey A. Tyganov, Ksenia V. Sergeeva, Vitaly Y. Kalashnikov, Ekaterina P. Kalashnikova, Timur M. Mirzoev, Grigoriy R. Kalamkarov, Tatiana F. Shevchenko and Boris S. Shenkman
Curr. Issues Mol. Biol. 2023, 45(7), 5613-5630; https://doi.org/10.3390/cimb45070354 - 30 Jun 2023
Cited by 1 | Viewed by 846
Abstract
Skeletal muscle disuse leads to pathological muscle activity as well as to slow-to-fast fiber-type transformation. Fast-type fibers are more fatigable than slow-type, so this transformation leads to a decline in muscle function. Prochlorperazine injections previously were shown to attenuate autonomous rat soleus muscle [...] Read more.
Skeletal muscle disuse leads to pathological muscle activity as well as to slow-to-fast fiber-type transformation. Fast-type fibers are more fatigable than slow-type, so this transformation leads to a decline in muscle function. Prochlorperazine injections previously were shown to attenuate autonomous rat soleus muscle electrical activity under unloading conditions. In this study, we found that prochlorperazine blocks slow-to-fast fiber-type transformation in disused skeletal muscles of rats, possibly through affecting calcium and ROS-related signaling. Full article
(This article belongs to the Special Issue Studying the Function of RNAs Using Omics Approaches)
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21 pages, 4018 KiB  
Article
RNA Methyltransferase METTL16’s Protein Domains Have Differential Functional Effects on Cell Processes
by Emily S. Talic, Ashley Wooten, Tonya N. Zeczycki and Kyle D. Mansfield
Curr. Issues Mol. Biol. 2023, 45(7), 5460-5480; https://doi.org/10.3390/cimb45070346 - 29 Jun 2023
Viewed by 957
Abstract
METTL16, a human m6A RNA methyltransferase, is currently known for its modification of U6 and MAT2A RNAs. Several studies have identified additional RNAs to which METTL16 binds, however whether METTL16 modifies these RNAs is still in question. Moreover, a recent study determined that [...] Read more.
METTL16, a human m6A RNA methyltransferase, is currently known for its modification of U6 and MAT2A RNAs. Several studies have identified additional RNAs to which METTL16 binds, however whether METTL16 modifies these RNAs is still in question. Moreover, a recent study determined that METTL16 contains more than one RNA-binding domain, leaving the importance of each individual RNA-binding domain unknown. Here we examined the effects of mutating the METTL16 protein in certain domains on overall cell processes. We chose to mutate the N-terminal RNA-binding domain, the methyltransferase domain, and the C-terminal RNA-binding domain. With these mutants, we identified changes in RNA-binding ability, protein and RNA expression, cell cycle phase occupancy, and proliferation. From the resulting changes in RNA and protein expression, we saw effects on cell cycle, metabolism, intracellular transport, and RNA processing pathways, which varied between the METTL16 mutant lines. We also saw significant effects on the G1 and S phase occupancy times and proliferative ability with some but not all the mutants. We have therefore concluded that while METTL16 may or may not m6A-modify all RNAs it binds, its binding (or lack of) has a significant outcome on a variety of cell processes. Full article
(This article belongs to the Special Issue Studying the Function of RNAs Using Omics Approaches)
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14 pages, 2220 KiB  
Article
Selective Concurrence of the Long Non-Coding RNA MALAT1 and the Polycomb Repressive Complex 2 to Promoter Regions of Active Genes in MCF7 Breast Cancer Cells
by Felipe Arratia, Cristopher Fierro, Alejandro Blanco, Sebastian Fuentes, Daniela Nahuelquen, Martin Montecino, Adriana Rojas and Rodrigo Aguilar
Curr. Issues Mol. Biol. 2023, 45(6), 4735-4748; https://doi.org/10.3390/cimb45060301 - 30 May 2023
Cited by 2 | Viewed by 1657
Abstract
In cancer cells, the long non-coding RNA (lncRNA) MALAT1 has arisen as a key partner for the Polycomb Repressive Complex 2 (PRC2), an epigenetic modifier. However, it is unknown whether this partnership occurs genome-wide at the chromatin level, as most of the studies [...] Read more.
In cancer cells, the long non-coding RNA (lncRNA) MALAT1 has arisen as a key partner for the Polycomb Repressive Complex 2 (PRC2), an epigenetic modifier. However, it is unknown whether this partnership occurs genome-wide at the chromatin level, as most of the studies focus on single genes that are usually repressed. Due to the genomic binding properties of both macromolecules, we wondered whether there are binding sites shared by PRC2 and MALAT1. Using public genome-binding datasets for PRC2 and MALAT1 derived from independent ChIP- and CHART-seq experiments performed with the breast cancer cell line MCF7, we searched for regions containing PRC2 and MALAT1 overlapping peaks. Peak calls for each molecule were performed using MACS2 and then overlapping peaks were identified by bedtools intersect. Using this approach, we identified 1293 genomic sites where PRC2 and MALAT1 concur. Interestingly, 54.75% of those sites are within gene promoter regions (<3000 bases from the TSS). These analyses were also linked with the transcription profiles of MCF7 cells, obtained from public RNA-seq data. Hence, it is suggested that MALAT1 and PRC2 can concomitantly bind to promoters of actively-transcribed genes in MCF7 cells. Gene ontology analyses revealed an enrichment of genes related to categories including cancer malignancy and epigenetic regulation. Thus, by re-visiting occupancy and transcriptomic data, we identified a key gene subset controlled by the collaboration of MALAT1 and PRC2. Full article
(This article belongs to the Special Issue Studying the Function of RNAs Using Omics Approaches)
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19 pages, 7266 KiB  
Article
Transcriptome Sequencing Reveals Salmonella Flagellin Activation of Interferon-β-Related Immune Responses in Macrophages
by Li Song, Dan Xiong, Yaya Wen, Ruimeng Tan, Xilong Kang, Xinan Jiao and Zhiming Pan
Curr. Issues Mol. Biol. 2023, 45(4), 2798-2816; https://doi.org/10.3390/cimb45040183 - 27 Mar 2023
Viewed by 1190
Abstract
The flagellin (FliC) of Salmonella typhimurium is a potential vaccine adjuvant as it can activate innate immunity and promote acquired immune responses. Macrophages are an important component of the innate immune system. The mechanism of flagellin’s adjuvant activity has been shown to be [...] Read more.
The flagellin (FliC) of Salmonella typhimurium is a potential vaccine adjuvant as it can activate innate immunity and promote acquired immune responses. Macrophages are an important component of the innate immune system. The mechanism of flagellin’s adjuvant activity has been shown to be related to its ability to activate macrophages. However, few studies have comprehensively investigated the effects of Salmonella flagellin in macrophages using transcriptome sequencing. In this study, RNA-Seq was used to analyze the expression patterns of RAW264.7 macrophages induced by FliC to identify novel transcriptomic signatures in macrophages. A total of 2204 differentially expressed genes were found in the FliC-treated group compared with the control. Gene ontology and KEGG pathway analyses identified the top significantly regulated functional classification and canonical pathways, which were mainly related to immune responses and regulation. Inflammatory cytokines (IL-6, IL-1β, TNF-α, etc.) and chemokines (CXCL2, CXCL10, CCL2, etc.) were highly expressed in RAW264.7 cells following stimulation. Notably, flagellin significantly increased the expression of interferon (IFN)-β. In addition, previously unidentified IFN regulatory factors (IRFs) and IFN-stimulated genes (ISGs) were also significantly upregulated. The results of RNA-Seq were verified, and furthermore, we demonstrated that flagellin increased the expression of IFN-β and IFN-related genes (IRFs and ISGs) in bone marrow-derived dendritic cells and macrophages. These results suggested that Salmonella flagellin can activate IFN-β-related immune responses in macrophages, which provides new insight into the immune mechanisms of flagellin adjuvant. Full article
(This article belongs to the Special Issue Studying the Function of RNAs Using Omics Approaches)
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17 pages, 3838 KiB  
Article
Change in Long Non-Coding RNA Expression Profile Related to the Antagonistic Effect of Clostridium perfringens Type C on Piglet Spleen
by Zunqiang Yan, Pengfei Wang, Qiaoli Yang, Xiaoli Gao, Shuangbao Gun and Xiaoyu Huang
Curr. Issues Mol. Biol. 2023, 45(3), 2309-2325; https://doi.org/10.3390/cimb45030149 - 09 Mar 2023
Cited by 1 | Viewed by 1137
Abstract
LncRNAs play important roles in resisting bacterial infection via host immune and inflammation responses. Clostridium perfringens (C. perfringens) type C is one of the main bacteria causing piglet diarrhea diseases, leading to major economic losses in the pig industry worldwide. In [...] Read more.
LncRNAs play important roles in resisting bacterial infection via host immune and inflammation responses. Clostridium perfringens (C. perfringens) type C is one of the main bacteria causing piglet diarrhea diseases, leading to major economic losses in the pig industry worldwide. In our previous studies, piglets resistant (SR) and susceptible (SS) to C. perfringens type C were identified based on differences in host immune capacity and total diarrhea scores. In this paper, the RNA-Seq data of the spleen were comprehensively reanalyzed to investigate antagonistic lncRNAs. Thus, 14 lncRNAs and 89 mRNAs were differentially expressed (DE) between the SR and SS groups compared to the control (SC) group. GO term enrichment, KEGG pathway enrichment and lncRNA-mRNA interactions were analyzed to identify four key lncRNA targeted genes via MAPK and NF-κB pathways to regulate cytokine genes (such as TNF-α and IL-6) against C. perfringens type C infection. The RT-qPCR results for six selected DE lncRNAs and mRNAs are consistent with the RNA-Seq data. This study analyzed the expression profiling of lncRNAs in the spleen of antagonistic and sensitive piglets and found four key lncRNAs against C. perfringens type C infection. The identification of antagonistic lncRNAs can facilitate investigations into the molecular mechanisms underlying resistance to diarrhea in piglets. Full article
(This article belongs to the Special Issue Studying the Function of RNAs Using Omics Approaches)
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18 pages, 2663 KiB  
Article
Identification of a miRNA Panel with a Potential Determinant Role in Patients Suffering from Periodontitis
by Oana Baru, Lajos Raduly, Cecilia Bica, Paul Chiroi, Liviuta Budisan, Nikolay Mehterov, Cristina Ciocan, Laura Ancuta Pop, Smaranda Buduru, Cornelia Braicu, Mandra Badea and Ioana Berindan-Neagoe
Curr. Issues Mol. Biol. 2023, 45(3), 2248-2265; https://doi.org/10.3390/cimb45030145 - 08 Mar 2023
Cited by 1 | Viewed by 1197
Abstract
In recent years, the role of microRNA (miRNA) in post-transcriptional gene regulation has advanced and supports strong evidence related to their important role in the regulation of a wide range of fundamental biological processes. Our study focuses on identifying specific alterations of miRNA [...] Read more.
In recent years, the role of microRNA (miRNA) in post-transcriptional gene regulation has advanced and supports strong evidence related to their important role in the regulation of a wide range of fundamental biological processes. Our study focuses on identifying specific alterations of miRNA patterns in periodontitis compared with healthy subjects. In the present study, we mapped the major miRNAs altered in patients with periodontitis (n = 3) compared with healthy subjects (n = 5), using microarray technology followed by a validation step by qRT-PCR and Ingenuity Pathways Analysis. Compared to healthy subjects, 159 differentially expressed miRNAs were identified among periodontitis patients, of which 89 were downregulated, and 70 were upregulated, considering a fold change of ±1.5 as the cut-off value and p ≤ 0.05. Key angiogenic miRNAs (miR-191-3p, miR-221-3p, miR-224-5p, miR-1228-3p) were further validated on a separate cohort of patients with periodontitis versus healthy controls by qRT-PCR, confirming the microarray data. Our findings indicate a periodontitis-specific miRNA expression pattern representing an essential issue for testing new potential diagnostic or prognostic biomarkers for periodontal disease. The identified miRNA profile in periodontal gingival tissue was linked to angiogenesis, with an important molecular mechanism that orchestrates cell fate. Full article
(This article belongs to the Special Issue Studying the Function of RNAs Using Omics Approaches)
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13 pages, 2386 KiB  
Article
Identification of miR-671-5p and Its Related Pathways as General Mechanisms of Both Form-Deprivation and Lens-Induced Myopia in Mice
by Zedu Cui, Yuke Huang, Xi Chen, Taiwei Chen, Xiangtao Hou, Na Yu, Yan Li, Jin Qiu, Pei Chen, Keming Yu and Jing Zhuang
Curr. Issues Mol. Biol. 2023, 45(3), 2060-2072; https://doi.org/10.3390/cimb45030132 - 02 Mar 2023
Cited by 1 | Viewed by 1374
Abstract
Animal models have been indispensable in shaping the understanding of myopia mechanisms, with form-deprivation myopia (FDM) and lens-induced myopia (LIM) being the most utilized. Similar pathological outcomes suggest that these two models are under the control of shared mechanisms. miRNAs play an important [...] Read more.
Animal models have been indispensable in shaping the understanding of myopia mechanisms, with form-deprivation myopia (FDM) and lens-induced myopia (LIM) being the most utilized. Similar pathological outcomes suggest that these two models are under the control of shared mechanisms. miRNAs play an important role in pathological development. Herein, based on two miRNA datasets (GSE131831 and GSE84220), we aimed to reveal the general miRNA changes involved in myopia development. After a comparison of the differentially expressed miRNAs, miR-671-5p was identified as the common downregulated miRNA in the retina. miR-671-5p is highly conserved and related to 40.78% of the target genes of all downregulated miRNAs. Moreover, 584 target genes of miR-671-5p are related to myopia, from which we further identified 8 hub genes. Pathway analysis showed that these hub genes are enriched in visual learning and extra-nuclear estrogen signaling. Furthermore, two of the hub genes are also targeted by atropine, which strongly supports a key role of miR-671-5p in myopic development. Finally, Tead1 was identified as a possible upstream regulator of miR-671-5p in myopia development. Overall, our study identified the general regulatory role of miR-671-5p in myopia as well as its upstream and downstream mechanisms and provided novel treatment targets, which might inspire future studies. Full article
(This article belongs to the Special Issue Studying the Function of RNAs Using Omics Approaches)
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16 pages, 2762 KiB  
Article
Impact of the m.13513G>A Variant on the Functions of the OXPHOS System and Cell Retrograde Signaling
by Dita Kidere, Pawel Zayakin, Diana Livcane, Marina Makrecka-Kuka, Janis Stavusis, Baiba Lace, Tsu-Kung Lin, Chia-Wei Liou and Inna Inashkina
Curr. Issues Mol. Biol. 2023, 45(3), 1794-1809; https://doi.org/10.3390/cimb45030115 - 22 Feb 2023
Viewed by 1367
Abstract
Mitochondria are involved in many vital functions in living cells, including the synthesis of ATP by oxidative phosphorylation (OXPHOS) and regulation of nuclear gene expression through retrograde signaling. Leigh syndrome is a heterogeneous neurological disorder resulting from an isolated complex I deficiency that [...] Read more.
Mitochondria are involved in many vital functions in living cells, including the synthesis of ATP by oxidative phosphorylation (OXPHOS) and regulation of nuclear gene expression through retrograde signaling. Leigh syndrome is a heterogeneous neurological disorder resulting from an isolated complex I deficiency that causes damage to mitochondrial energy production. The pathogenic mitochondrial DNA (mtDNA) variant m.13513G>A has been associated with Leigh syndrome. The present study investigated the effects of this mtDNA variant on the OXPHOS system and cell retrograde signaling. Transmitochondrial cytoplasmic hybrid (cybrid) cell lines harboring 50% and 70% of the m.13513G>A variant were generated and tested along with wild-type (WT) cells. The functionality of the OXPHOS system was evaluated by spectrophotometric assessment of enzyme activity and high-resolution respirometry. Nuclear gene expression was investigated by RNA sequencing and droplet digital PCR. Increasing levels of heteroplasmy were associated with reduced OXPHOS system complex I, IV, and I + III activities, and high-resolution respirometry also showed a complex I defect. Profound changes in transcription levels of nuclear genes were observed in the cell lines harboring the pathogenic mtDNA variant, indicating the physiological processes associated with defective mitochondria. Full article
(This article belongs to the Special Issue Studying the Function of RNAs Using Omics Approaches)
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11 pages, 2030 KiB  
Article
Cooperative Binding of SRSF3 to Structured 3’ss-α Exon RNA during α Exon Inclusion in the ZO-1 mRNA
by Tea Anastasia Ruiz-Luis, Carlos Ortuño-Pineda, José Manuel Galindo-Rosales, Odila Saucedo-Cárdenas and Jesús Valdés
Curr. Issues Mol. Biol. 2023, 45(1), 593-603; https://doi.org/10.3390/cimb45010039 - 09 Jan 2023
Viewed by 1449
Abstract
ZO-1α+ and ZO-1α− proteins are expressed in hermetic and leaky tight junctions, respectively. Two cis-acting distant exonic elements partly activate the 240 nucleotide-long α exon producing the ZO-1α+ isoform. However, the elements within and around the α exon and their respective factors involved [...] Read more.
ZO-1α+ and ZO-1α− proteins are expressed in hermetic and leaky tight junctions, respectively. Two cis-acting distant exonic elements partly activate the 240 nucleotide-long α exon producing the ZO-1α+ isoform. However, the elements within and around the α exon and their respective factors involved in its splicing are unknown. To study the dynamic interaction between SRSF3 and its bioinformatically predicted target sites around the 3’ss upstream of the α exon during its activation, we performed EMSA, crosslinking, and in vivo splicing assays by ZO-1 minigene expression and siRNA-mediated silencing in transfected cells. Using V1 RNase, we probed the possible formation of a hairpin RNA structure between the intronic and proximal exonic SRSF3 binding sites. The hairpin sufficed for complex formations in the EMSA. The interaction of SRSF3 with the intronic site promoted the cooperative binding of SRSF3 to the exonic site. Finally, SRSF3 restored α exon activation in SRSF3 knockdown transfectants. Altogether, our results show that SRSF3–hairpin RNA interaction is crucial in the early recognition of 3’ss for α exon activation. It remains to be explored whether SRSF3 recruits or stabilizes the binding of other factors or brings separate splice sites into proximity. Full article
(This article belongs to the Special Issue Studying the Function of RNAs Using Omics Approaches)
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Review

Jump to: Research, Other

15 pages, 2304 KiB  
Review
Revealing the History and Mystery of RNA-Seq
by Aishwarya Gondane and Harri M. Itkonen
Curr. Issues Mol. Biol. 2023, 45(3), 1860-1874; https://doi.org/10.3390/cimb45030120 - 24 Feb 2023
Cited by 5 | Viewed by 3794
Abstract
Advances in RNA-sequencing technologies have led to the development of intriguing experimental setups, a massive accumulation of data, and high demand for tools to analyze it. To answer this demand, computational scientists have developed a myriad of data analysis pipelines, but it is [...] Read more.
Advances in RNA-sequencing technologies have led to the development of intriguing experimental setups, a massive accumulation of data, and high demand for tools to analyze it. To answer this demand, computational scientists have developed a myriad of data analysis pipelines, but it is less often considered what the most appropriate one is. The RNA-sequencing data analysis pipeline can be divided into three major parts: data pre-processing, followed by the main and downstream analyses. Here, we present an overview of the tools used in both the bulk RNA-seq and at the single-cell level, with a particular focus on alternative splicing and active RNA synthesis analysis. A crucial part of data pre-processing is quality control, which defines the necessity of the next steps; adapter removal, trimming, and filtering. After pre-processing, the data are finally analyzed using a variety of tools: differential gene expression, alternative splicing, and assessment of active synthesis, the latter requiring dedicated sample preparation. In brief, we describe the commonly used tools in the sample preparation and analysis of RNA-seq data. Full article
(This article belongs to the Special Issue Studying the Function of RNAs Using Omics Approaches)
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Other

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24 pages, 1673 KiB  
Perspective
Perspective for Studying the Relationship of miRNAs with Transposable Elements
by Rustam Nailevich Mustafin and Elza Khusnutdinova
Curr. Issues Mol. Biol. 2023, 45(4), 3122-3145; https://doi.org/10.3390/cimb45040204 - 05 Apr 2023
Cited by 4 | Viewed by 1948
Abstract
Transposable elements are important sources of miRNA, long non-coding RNAs genes, and their targets in the composition of protein-coding genes in plants and animals. Therefore, the detection of expression levels of specific non-coding RNAs in various tissues and cells in normal and pathological [...] Read more.
Transposable elements are important sources of miRNA, long non-coding RNAs genes, and their targets in the composition of protein-coding genes in plants and animals. Therefore, the detection of expression levels of specific non-coding RNAs in various tissues and cells in normal and pathological conditions may indicate a programmed pattern of transposable elements’ activation. This reflects the species-specific composition and distribution of transposable elements in genomes, which underlie gene regulation in every cell division, including during aging. TEs’ expression is also regulated by epigenetic factors (DNA methylation, histone modifications), SIRT6, cytidine deaminases APOBEC3, APOBEC1, and other catalytic proteins, such as ERCC, TREX1, RB1, HELLS, and MEGP2. In evolution, protein-coding genes and their regulatory elements are derived from transposons. As part of non-coding regions and introns of genes, they are sensors for transcriptional and post-transcriptional control of expression, using miRNAs and long non-coding RNAs, that arose from transposable elements in evolution. Methods (Orbld, ncRNAclassifier) and databases have been created for determining the occurrence of miRNAs from transposable elements in plants (PlanTE-MIR DB, PlaNC-TE), which can be used to design epigenetic gene networks in ontogenesis. Based on the data accumulated in the scientific literature, the presence of 467 transposon-derived miRNA genes in the human genome has been reliably established. It was proposed to create an updated and controlled online bioinformatics database of miRNAs derived from transposable elements in healthy individuals, as well as expression changes of these miRNAs during aging and various diseases, such as cancer and difficult-to-treat diseases. The use of the information obtained can open new horizons in the management of tissue and organ differentiation to aging slow down. In addition, the created database could become the basis for clarifying the mechanisms of pathogenesis of various diseases (imbalance in the activity of transposable elements, reflected in changes in the expression of miRNAs) and designing their targeted therapy using specific miRNAs as targets. This article provides examples of the detection of transposable elements-derived miRNAs involved in the development of specific malignant neoplasms, aging, and idiopathic pulmonary fibrosis. Full article
(This article belongs to the Special Issue Studying the Function of RNAs Using Omics Approaches)
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