Non-coding RNA in the USA: Latest Advances and Perspectives

A special issue of Non-Coding RNA (ISSN 2311-553X).

Deadline for manuscript submissions: closed (25 July 2023) | Viewed by 12687

Special Issue Editors

Department of Biology, University of Pennsylvania, 433 S, University Ave, Philadelphia, PA 19104, USA
Interests: RNA silencing; RNA secondary structure; microRNAs; RNA-protein interactions; post-transcriptional gene regulation
Department of Medical Genetics and Molecular Biochemistry, Lewis Katz School of Medicine, Temple University, Philadelphia, PA 19140, USA
Interests: lnRNA
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

The purpose of this Special Issue is to present a series of articles (both reviews and original research) from experts in non-coding RNA research across the USA. We invite the submission of articles that highlight the history and deepen our current understanding of the role of non-coding RNA (both small and long) in multiple disciplines and organisms ranging from bacteria to plant and human cells. Potential topics include, but are not limited:

  • Non-coding RNA processing;
  • Non-coding RNA functions;
  • Functions of RNA modifications in coding and non-coding RNA;
  • Non-coding RNA structure;
  • Non-coding RNA regulation;
  • Non-coding RNA degradation;
  • Non-coding RNA biogenesis.

Prof. Dr. Brian D. Gregory
Prof. Dr. Ling Yang
Guest Editors

Manuscript Submission Information

Manuscripts should be submitted online at www.mdpi.com by registering and logging in to this website. Once you are registered, click here to go to the submission form. Manuscripts can be submitted until the deadline. All submissions that pass pre-check are peer-reviewed. Accepted papers will be published continuously in the journal (as soon as accepted) and will be listed together on the special issue website. Research articles, review articles as well as short communications are invited. For planned papers, a title and short abstract (about 100 words) can be sent to the Editorial Office for announcement on this website.

Submitted manuscripts should not have been published previously, nor be under consideration for publication elsewhere (except conference proceedings papers). All manuscripts are thoroughly refereed through a single-blind peer-review process. A guide for authors and other relevant information for submission of manuscripts is available on the Instructions for Authors page. Non-Coding RNA is an international peer-reviewed open access semimonthly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. The Article Processing Charge (APC) for publication in this open access journal is 1800 CHF (Swiss Francs). Submitted papers should be well formatted and use good English. Authors may use MDPI's English editing service prior to publication or during author revisions.

Keywords

  • RNA biology
  • long non-coding RNAs
  • small RNAs
  • microRNAs
  • circular RNAs
  • RNA modification in coding and ncRNAs
  • ncRNA structure
  • ncRNA regulation
  • ncRNA degradation

Published Papers (7 papers)

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Research

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15 pages, 3322 KiB  
Article
RNA N6-Methyladenosine Affects Copper-Induced Oxidative Stress Response in Arabidopsis thaliana
by Bishwas Sharma, Ganesan Govindan, Yongfang Li, Ramanjulu Sunkar and Brian D. Gregory
Non-Coding RNA 2024, 10(1), 8; https://doi.org/10.3390/ncrna10010008 - 19 Jan 2024
Viewed by 1253
Abstract
Recently, post-transcriptional regulation of mRNA mediated by N6-methyladenosine (m6A) has been found to have profound effects on transcriptome regulation during plant responses to various abiotic stresses. However, whether this RNA modification can affect an oxidative stress response in plants [...] Read more.
Recently, post-transcriptional regulation of mRNA mediated by N6-methyladenosine (m6A) has been found to have profound effects on transcriptome regulation during plant responses to various abiotic stresses. However, whether this RNA modification can affect an oxidative stress response in plants has not been studied. To assess the role of m6A modifications during copper-induced oxidative stress responses, m6A-IP-seq was performed in Arabidopsis seedlings exposed to high levels of copper sulfate. This analysis revealed large-scale shifts in this modification on the transcripts most relevant for oxidative stress. This altered epitranscriptomic mark is known to influence transcript abundance and translation; therefore we scrutinized these possibilities. We found an increased abundance of copper-enriched m6A-containing transcripts. Similarly, we also found increased ribosome occupancy of copper-enriched m6A-containing transcripts, specifically those encoding proteins involved with stress responses relevant to oxidative stressors. Furthermore, the significance of the m6A epitranscriptome on plant oxidative stress tolerance was uncovered by assessing germination and seedling development of the mta (N6-methyladenosine RNA methyltransferase A mutant complemented with ABI3:MTA) mutant exposed to high copper treatment. These analyses suggested hypersensitivity of the mta mutant compared to the wild-type plants in response to copper-induced oxidative stress. Overall, our findings suggest an important role for m6A in the oxidative stress response of Arabidopsis. Full article
(This article belongs to the Special Issue Non-coding RNA in the USA: Latest Advances and Perspectives)
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21 pages, 3568 KiB  
Article
Sequencing Reveals miRNAs Enriched in the Developing Mouse Enteric Nervous System
by Christopher Pai, Rajarshi Sengupta and Robert O. Heuckeroth
Non-Coding RNA 2024, 10(1), 1; https://doi.org/10.3390/ncrna10010001 - 22 Dec 2023
Viewed by 1671
Abstract
The enteric nervous system (ENS) is an essential network of neurons and glia in the bowel wall. Defects in ENS development can result in Hirschsprung disease (HSCR), a life-threatening condition characterized by severe constipation, abdominal distention, bilious vomiting, and failure to thrive. A [...] Read more.
The enteric nervous system (ENS) is an essential network of neurons and glia in the bowel wall. Defects in ENS development can result in Hirschsprung disease (HSCR), a life-threatening condition characterized by severe constipation, abdominal distention, bilious vomiting, and failure to thrive. A growing body of literature connects HSCR to alterations in miRNA expression, but there are limited data on the normal miRNA landscape in the developing ENS. We sequenced small RNAs (smRNA-seq) and messenger RNAs (mRNA-seq) from ENS precursor cells of mid-gestation Ednrb-EGFP mice and compared them to aggregated RNA from all other cells in the developing bowel. Our smRNA-seq results identified 73 miRNAs that were significantly enriched and highly expressed in the developing ENS, with miR-9, miR-27b, miR-124, miR-137, and miR-488 as our top 5 miRNAs that are conserved in humans. However, contrary to prior reports, our follow-up analyses of miR-137 showed that loss of Mir137 in Nestin-cre, Wnt1-cre, Sox10-cre, or Baf53b-cre lineage cells had no effect on mouse survival or ENS development. Our data provide important context for future studies of miRNAs in HSCR and other ENS diseases and highlight open questions about facility-specific factors in development. Full article
(This article belongs to the Special Issue Non-coding RNA in the USA: Latest Advances and Perspectives)
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19 pages, 3509 KiB  
Article
Age and 17β-Estradiol (E2) Facilitate Nuclear Export and Argonaute Loading of microRNAs in the Female Brain
by Megan L. Linscott, Yoldas Yildiz, Sarah Flury, Mikayla L. Newby and Toni R. Pak
Non-Coding RNA 2023, 9(6), 74; https://doi.org/10.3390/ncrna9060074 - 06 Dec 2023
Cited by 1 | Viewed by 1580
Abstract
Aging in women is accompanied by a dramatic change in circulating sex steroid hormones. Specifically, the primary circulating estrogen, 17β-estradiol (E2), is nearly undetectable in post-menopausal women. This decline is associated with a variety of cognitive and mood disorders, yet hormone [...] Read more.
Aging in women is accompanied by a dramatic change in circulating sex steroid hormones. Specifically, the primary circulating estrogen, 17β-estradiol (E2), is nearly undetectable in post-menopausal women. This decline is associated with a variety of cognitive and mood disorders, yet hormone replacement therapy is only effective within a narrow window of time surrounding the menopausal transition. Our previous work identified microRNAs as a potential molecular substrate underlying the change in E2 efficacy associated with menopause in advanced age. Specifically, we showed that E2 regulated a small subset of mature miRNAs in the aging female brain. In this study, we hypothesized that E2 regulates the stability of mature miRNAs by altering their subcellular localization and their association with argonaute proteins. We also tested the hypothesis that the RNA binding protein, hnRNP A1, was an important regulator of mature miR-9-5p expression in neuronal cells. Our results demonstrated that E2 treatment affected miRNA subcellular localization and its association with argonaute proteins differently, depending on the length of time following E2 deprivation (i.e., ovariectomy). We also provide strong evidence that hnRNP A1 regulates the transcription of pri-miR-9 and likely plays a posttranscriptional role in mature miR-9-5p turnover. Taken together, these data have important implications for considering the optimal timing for hormone replacement therapy, which might be less dependent on age and more related to how long treatment is delayed following menopause. Full article
(This article belongs to the Special Issue Non-coding RNA in the USA: Latest Advances and Perspectives)
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13 pages, 1407 KiB  
Article
Effects of Controlled Ozone Exposure on Circulating microRNAs and Vascular and Coagulation Biomarkers: A Mediation Analysis
by Hao Chen, Syed Masood, Ana G. Rappold, David Diaz-Sanchez, James M. Samet and Haiyan Tong
Non-Coding RNA 2023, 9(4), 43; https://doi.org/10.3390/ncrna9040043 - 01 Aug 2023
Viewed by 1110
Abstract
Exposure to ozone (O3) is associated with adverse respiratory and cardiovascular outcomes. Alterations in circulating microRNAs (miRNAs) may contribute to the adverse vascular effects of O3 exposure through inter-cellular communication resulting in post-transcriptional regulation of messenger RNAs by miRNAs. In [...] Read more.
Exposure to ozone (O3) is associated with adverse respiratory and cardiovascular outcomes. Alterations in circulating microRNAs (miRNAs) may contribute to the adverse vascular effects of O3 exposure through inter-cellular communication resulting in post-transcriptional regulation of messenger RNAs by miRNAs. In this study, we investigated whether O3 exposure induces alterations in circulating miRNAs that can mediate effects on downstream vascular and coagulation biomarkers. Twenty-three healthy male adults were exposed on successive days to filtered air and 300 ppb O3 for 2 h. Circulating miRNA and protein biomarkers were quantified after each exposure session. The data were subjected to mixed-effects model and mediation analyses for the statistical analyses. The results showed that the expression level of multiple circulating miRNAs (e.g., miR-19a-3p, miR-34a-5p) was significantly associated with O3 exposure. Pathway analysis showed that these miRNAs were predictive of changing levels of downstream biomarkers [e.g., D-dimer, C-reactive protein, tumor necrosis factor α (TNFα)]. Mediation analysis showed that miR-19a-3p may be a significant mediator of O3-exposure-induced changes in blood TNFα levels [0.08 (0.01, 0.15), p = 0.02]. In conclusion, this preliminary study showed that O3 exposure of healthy male adults resulted in changes in circulating miRNAs, some of which may mediate vascular effects of O3 exposure. Full article
(This article belongs to the Special Issue Non-coding RNA in the USA: Latest Advances and Perspectives)
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15 pages, 1814 KiB  
Article
Liquid Biopsies Poorly miRror Renal Ischemia-Reperfusion Injury
by Adaysha C. Williams, Vaishali Singh, Pengyuan Liu and Alison J. Kriegel
Non-Coding RNA 2023, 9(2), 24; https://doi.org/10.3390/ncrna9020024 - 01 Apr 2023
Viewed by 1526
Abstract
Acute kidney injury (AKI) is the rapid reduction in renal function. It is often difficult to detect at an early stage. Biofluid microRNAs (miRs) have been proposed as novel biomarkers due to their regulatory role in renal pathophysiology. The goal of this study [...] Read more.
Acute kidney injury (AKI) is the rapid reduction in renal function. It is often difficult to detect at an early stage. Biofluid microRNAs (miRs) have been proposed as novel biomarkers due to their regulatory role in renal pathophysiology. The goal of this study was to determine the overlap in AKI miRNA profiles in the renal cortex, urine, and plasma samples collected from a rat model of ischemia-reperfusion (IR)-induced AKI. Bilateral renal ischemia was induced by clamping the renal pedicles for 30 min, followed by reperfusion. Urine was then collected over 24 h, followed by terminal blood and tissue collection for small RNA profiling. Differentially expressed (IR vs. sham) miRs within the urine and renal cortex sample types demonstrated a strong correlation in normalized abundance regardless of injury (IR and sham: R2 = 0.8710 and 0.9716, respectively). Relatively few miRs were differentially expressed in multiple samples. Further, there were no differentially expressed miRs with clinically relevant sequence conservation common between renal cortex and urine samples. This project highlights the need for a comprehensive analysis of potential miR biomarkers, including analysis of pathological tissues and biofluids, with the goal of identifying the cellular origin of altered miRs. Analysis at earlier timepoints is needed to further evaluate clinical potential. Full article
(This article belongs to the Special Issue Non-coding RNA in the USA: Latest Advances and Perspectives)
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11 pages, 2586 KiB  
Article
LncRNA MALAT1 Regulates Hyperglycemia Induced EMT in Keratinocyte via miR-205
by Liping Zhang, George Chu-Chih Hung, Songmei Meng, Robin Evans and Junwang Xu
Non-Coding RNA 2023, 9(1), 14; https://doi.org/10.3390/ncrna9010014 - 11 Feb 2023
Cited by 1 | Viewed by 1648
Abstract
Epithelial-to-mesenchymal transition (EMT) is critical to cutaneous wound healing. When skin is injured, EMT activates and mobilizes keratinocytes toward the wound bed, therefore enabling re-epithelialization. This process becomes dysregulated in patients with diabetes mellitus (DM). Long non-coding RNAs (lncRNAs) regulate many biological processes. [...] Read more.
Epithelial-to-mesenchymal transition (EMT) is critical to cutaneous wound healing. When skin is injured, EMT activates and mobilizes keratinocytes toward the wound bed, therefore enabling re-epithelialization. This process becomes dysregulated in patients with diabetes mellitus (DM). Long non-coding RNAs (lncRNAs) regulate many biological processes. LncRNA-metastasis-associated lung adenocarcinoma transcript 1 (MALAT1) influences numerous cellular processes, including EMT. The objective of the current study is to explore the role of MALAT1 in hyperglycemia (HG)-induced EMT. The expression of MALAT1 was found to be significantly upregulated, while the expression of miR-205 was downregulated in diabetic wounds and high-glucose-treated HaCaT cells. The initiation of EMT in HaCaT cells from hyperglycemia was confirmed by a morphological change, the increased expression of CDH2, KRT10, and ACTA2, and the downregulation of CDH1. The knockdown of MALAT1 was achieved by transfecting a small interfering RNA (SiRNA). MALAT1 and miR-205 were found to modulate HG-induced EMT. MALAT1 silencing or miR-205 overexpression appears to attenuate hyperglycemia-induced EMT. Mechanistically, MALAT1 affects HG-induced EMT through binding to miR-205 and therefore inducing ZEB1, a critical transcription factor for EMT. In summary, lncRNA MALAT1 is involved in the hyperglycemia-induced EMT of human HaCaT cells. This provides a new perspective on the pathogenesis of diabetic wounds. Full article
(This article belongs to the Special Issue Non-coding RNA in the USA: Latest Advances and Perspectives)
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Review

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16 pages, 1328 KiB  
Review
Exosome RNA Sequencing as a Tool in the Search for Cancer Biomarkers
by Marina Elkommos-Zakhary, Neeraja Rajesh and Vladimir Beljanski
Non-Coding RNA 2022, 8(6), 75; https://doi.org/10.3390/ncrna8060075 - 09 Nov 2022
Cited by 4 | Viewed by 3116
Abstract
Numerous noninvasive methods are currently being used to determine biomarkers for diseases such as cancer. However, these methods are not always precise and reliable. Thus, there is an unmet need for better diagnostic and prognostic biomarkers that will be used to diagnose cancer [...] Read more.
Numerous noninvasive methods are currently being used to determine biomarkers for diseases such as cancer. However, these methods are not always precise and reliable. Thus, there is an unmet need for better diagnostic and prognostic biomarkers that will be used to diagnose cancer in early, more treatable stages of the disease. Exosomes are extracellular vesicles of endocytic origin released by the majority of cells. Exosomes contain and transport nucleic acids, proteins, growth factors, and cytokines from their parent cells to surrounding or even distant cells via circulation in biofluids. Exosomes have attracted the interest of researchers, as recent data indicate that exosome content may be indicative of disease stages and may contribute to disease progression via exosome-mediated extracellular communication. Therefore, the contents of these vesicles are being investigated as possible biomarkers for disease diagnosis and prognosis. The functions of exosomes and their contents in disease development are becoming clearer as isolation and analytical methods, such as RNA sequencing, advance. In this review, we discuss current advances and challenges in exosomal content analyses with emphasis on information that can be generated using RNA sequencing. We also discuss how the RNA sequencing of exosomes may be used to discover novel biomarkers for the detection of different stages for various cancers using specific microRNAs that were found to be differentially expressed between healthy controls and cancer-diagnosed subjects. Full article
(This article belongs to the Special Issue Non-coding RNA in the USA: Latest Advances and Perspectives)
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