ijms-logo

Journal Browser

Journal Browser

Interplay between Pre-mRNA Splicing and Other Gene Expression Steps in Eukaryotes

A special issue of International Journal of Molecular Sciences (ISSN 1422-0067). This special issue belongs to the section "Molecular Biology".

Deadline for manuscript submissions: closed (31 October 2019) | Viewed by 27993

Special Issue Editor


E-Mail Website
Guest Editor
Laboratory of Cellular Biochemistry, Department of Animal Resource Sciences, Graduate School of Agriculture and Life Sciences, Tokyo, Japan
Interests: pre-mRNA splicing; RNA processing; RNA diseases; gene expression; molecular links between mRNA splicing and other gene expression steps; signal transduction modulated by alternative splicing
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

In eukaryotes, RNAs transcribed from genomic DNA are subjected to many regulatory processes, indicating their pivotal role in gene expression. Pre-mRNA splicing is a process to remove introns and ligate exons so that mRNA can be produced. This step is critical for higher eukaryotes and is vigorously regulated. After finding the Exon Junction Complex, several lines of evidence have noted that pre-mRNA splicing and other gene expression steps have influence over each other and there is an interplay between pre-mRNA splicing and other gene expression in higher eukaryotes.

As the Guest Editor of this Special Issue, “Interplay between Pre-mRNA Splicing and Other Gene Expression Steps in Eukaryotes”, in IJMS, I expect submissions from many researchers working on the wide spectrum of physiological processes in which RNAs are involved. The focus of this topic is the molecular link between pre-mRNA splicing and other steps in eukaryotes. Examples for this Special Issue include transcription-coupled splicing, coupling of splicing and mRNA export/localization, nonsense-mediated mRNA decay, enhancement of translation, and signal transduction pathway modulation by alternative splicing. Manuscripts regarding splicing changes during the development of organisms and aberrant splicing in human diseases are also very welcome. The formats for submissions include original research reports, reviews/mini-reviews, perspectives/opinions and methodology articles.

Dr. Naoyuki Kataoka
Guest Editor

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. International Journal of Molecular Sciences is an international peer-reviewed open access semimonthly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. There is an Article Processing Charge (APC) for publication in this open access journal. For details about the APC please see here. 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

  • Pre-mRNA splicing
  • Exon Junction Complex
  • alternative splicing
  • transcription
  • translation
  • RNA export
  • RNA localization
  • RNA decay

Published Papers (6 papers)

Order results
Result details
Select all
Export citation of selected articles as:

Research

Jump to: Review

14 pages, 3083 KiB  
Article
Angiotensin II Influences Pre-mRNA Splicing Regulation by Enhancing RBM20 Transcription Through Activation of the MAPK/ELK1 Signaling Pathway
by Hanfang Cai, Chaoqun Zhu, Zhilong Chen, Rexiati Maimaiti, Mingming Sun, Richard J. McCormick, Xianyong Lan, Hong Chen and Wei Guo
Int. J. Mol. Sci. 2019, 20(20), 5059; https://doi.org/10.3390/ijms20205059 - 12 Oct 2019
Cited by 8 | Viewed by 3374
Abstract
RNA binding motif 20 (RBM20) is a key regulator of pre-mRNA splicing of titin and other genes that are associated with cardiac diseases. Hormones, like insulin, triiodothyronine (T3), and angiotensin II (Ang II), can regulate gene-splicing through RBM20, but the detailed mechanism remains [...] Read more.
RNA binding motif 20 (RBM20) is a key regulator of pre-mRNA splicing of titin and other genes that are associated with cardiac diseases. Hormones, like insulin, triiodothyronine (T3), and angiotensin II (Ang II), can regulate gene-splicing through RBM20, but the detailed mechanism remains unclear. This study was aimed at investigating the signaling mechanism by which hormones regulate pre-mRNA splicing through RBM20. We first examined the role of RBM20 in Z-, I-, and M-band titin splicing at different ages in wild type (WT) and RBM20 knockout (KO) rats using RT-PCR; we found that RBM20 is the predominant regulator of I-band titin splicing at all ages. Then we treated rats with propylthiouracil (PTU), T3, streptozotocin (STZ), and Ang II and evaluated the impact of these hormones on the splicing of titin, LIM domain binding 3 (Ldb3), calcium/calmodulin-dependent protein kinase II gamma (Camk2g), and triadin (Trdn). We determined the activation of mitogen-activated protein kinase (MAPK) signaling in primary cardiomyocytes treated with insulin, T3, and Ang II using western blotting; MAPK signaling was activated and RBM20 expression increased after treatment. Two downstream transcriptional factors c-jun and ETS Transcription Factor (ELK1) can bind the promoter of RBM20. A dual-luciferase activity assay revealed that Ang II, but not insulin and T3, can trigger ELK1 and thus promote transcription of RBM20. This study revealed that Ang II can trigger ELK1 through activation of MAPK signaling by enhancing RBM20 expression which regulates pre-mRNA splicing. Our study provides a potential therapeutic target for the treatment of cardiac diseases in RBM20-mediated pre-mRNA splicing. Full article
Show Figures

Figure 1

18 pages, 3045 KiB  
Article
Sex-Dimorphic Behavioral Alterations and Altered Neurogenesis in U12 Intron Splicing-Defective Zrsr1 Mutant Mice
by Francisco Alén, Isabel Gómez-Redondo, Patricia Rivera, Juan Suárez, Priscila Ramos-Ibeas, Eva Pericuesta, Raul Fernández-González, Serafín Perez-Cerezales, Keiko Horiuchi, Laura Orio, Fernando Rodriguez de Fonseca and Alfonso Gutiérrez-Adán
Int. J. Mol. Sci. 2019, 20(14), 3543; https://doi.org/10.3390/ijms20143543 - 19 Jul 2019
Cited by 10 | Viewed by 4024
Abstract
Mutant mice with respect to the splicing factor Zrsr1 present altered spermatogenesis and infertility. To investigate whether Zrsr1 is involved in the homeostatic control that the hypothalamus exerts over reproductive functions, we first analyzed both differential gene and isoform expression and alternative splicing [...] Read more.
Mutant mice with respect to the splicing factor Zrsr1 present altered spermatogenesis and infertility. To investigate whether Zrsr1 is involved in the homeostatic control that the hypothalamus exerts over reproductive functions, we first analyzed both differential gene and isoform expression and alternative splicing alterations in Zrsr1 mutant (Zrsr1mu) hypothalamus; second, we analyzed the spontaneous and social behavior of Zrsr1mu mice; and third, we analyzed adult cell proliferation and survival in the Zrsr1mu hypothalamus. The Zrsr1mu hypothalamus showed altered expression of genes and isoforms related to the glutathione metabolic process, synaptonemal complex assembly, mRNA transport, and altered splicing events involving the enrichment of U12-type intron retention (IR). Furthermore, increased IR in U12-containing genes related with the prolactin, progesterone, and gonadotropin-releasing hormone (GnRH) reproductive signaling pathway was observed. This was associated with a hyperactive phenotype in both males and females, with an anxious phenotype in females, and with increased social interaction in males, instead of the classical aggressive behavior. In addition, Zrsr1mu females but not males exhibited reduced cell proliferation in both the hypothalamus and the subventricular zone. Overall, these results suggest that Zrsr1 expression and function are relevant to organization of the hypothalamic cell network controlling behavior. Full article
Show Figures

Figure 1

18 pages, 3121 KiB  
Article
Dysregulation of Circular RNAs in Myotonic Dystrophy Type 1
by Christine Voellenkle, Alessandra Perfetti, Matteo Carrara, Paola Fuschi, Laura Valentina Renna, Marialucia Longo, Simona Baghai Sain, Rosanna Cardani, Rea Valaperta, Gabriella Silvestri, Ivano Legnini, Irene Bozzoni, Denis Furling, Carlo Gaetano, Germana Falcone, Giovanni Meola and Fabio Martelli
Int. J. Mol. Sci. 2019, 20(8), 1938; https://doi.org/10.3390/ijms20081938 - 19 Apr 2019
Cited by 24 | Viewed by 5315
Abstract
Circular RNAs (circRNAs) constitute a recently re-discovered class of non-coding RNAs functioning as sponges for miRNAs and proteins, affecting RNA splicing and regulating transcription. CircRNAs are generated by “back-splicing”, which is the linking covalently of 3′- and 5′-ends of exons. Thus, circRNA levels [...] Read more.
Circular RNAs (circRNAs) constitute a recently re-discovered class of non-coding RNAs functioning as sponges for miRNAs and proteins, affecting RNA splicing and regulating transcription. CircRNAs are generated by “back-splicing”, which is the linking covalently of 3′- and 5′-ends of exons. Thus, circRNA levels might be deregulated in conditions associated with altered RNA-splicing. Significantly, growing evidence indicates their role in human diseases. Specifically, myotonic dystrophy type 1 (DM1) is a multisystemic disorder caused by expanded CTG repeats in the DMPK gene which results in abnormal mRNA-splicing. In this investigation, circRNAs expressed in DM1 skeletal muscles were identified by analyzing RNA-sequencing data-sets followed by qPCR validation. In muscle biopsies, out of nine tested, four transcripts showed an increased circular fraction: CDYL, HIPK3, RTN4_03, and ZNF609. Their circular fraction values correlated with skeletal muscle strength and with splicing biomarkers of disease severity, and displayed higher values in more severely affected patients. Moreover, Receiver-Operating-Characteristics curves of these four circRNAs discriminated DM1 patients from controls. The identified circRNAs were also detectable in peripheral-blood-mononuclear-cells (PBMCs) and the plasma of DM1 patients, but they were not regulated significantly. Finally, increased circular fractions of RTN4_03 and ZNF609 were also observed in differentiated myogenic cell lines derived from DM1 patients. In conclusion, this pilot study identified circRNA dysregulation in DM1 patients. Full article
Show Figures

Graphical abstract

Review

Jump to: Research

22 pages, 1636 KiB  
Review
Isoforms of Base Excision Repair Enzymes Produced by Alternative Splicing
by Elizaveta O. Boldinova, Rafil F. Khairullin, Alena V. Makarova and Dmitry O. Zharkov
Int. J. Mol. Sci. 2019, 20(13), 3279; https://doi.org/10.3390/ijms20133279 - 3 Jul 2019
Cited by 12 | Viewed by 3262
Abstract
Transcripts of many enzymes involved in base excision repair (BER) undergo extensive alternative splicing, but functions of the corresponding alternative splice variants remain largely unexplored. In this review, we cover the studies describing the common alternatively spliced isoforms and disease-associated variants of DNA [...] Read more.
Transcripts of many enzymes involved in base excision repair (BER) undergo extensive alternative splicing, but functions of the corresponding alternative splice variants remain largely unexplored. In this review, we cover the studies describing the common alternatively spliced isoforms and disease-associated variants of DNA glycosylases, AP-endonuclease 1, and DNA polymerase beta. We also discuss the roles of alternative splicing in the regulation of their expression, catalytic activities, and intracellular transport. Full article
Show Figures

Figure 1

15 pages, 1596 KiB  
Review
Regulation of Gene Expression under Hypoxic Conditions
by Koh Nakayama and Naoyuki Kataoka
Int. J. Mol. Sci. 2019, 20(13), 3278; https://doi.org/10.3390/ijms20133278 - 3 Jul 2019
Cited by 60 | Viewed by 6274
Abstract
Eukaryotes are often subjected to different kinds of stress. In order to adjust to such circumstances, eukaryotes activate stress–response pathways and regulate gene expression. Eukaryotic gene expression consists of many different steps, including transcription, RNA processing, RNA transport, and translation. In this review [...] Read more.
Eukaryotes are often subjected to different kinds of stress. In order to adjust to such circumstances, eukaryotes activate stress–response pathways and regulate gene expression. Eukaryotic gene expression consists of many different steps, including transcription, RNA processing, RNA transport, and translation. In this review article, we focus on both transcriptional and post-transcriptional regulations of gene expression under hypoxic conditions. In the first part of the review, transcriptional regulations mediated by various transcription factors including Hypoxia-Inducible Factors (HIFs) are described. In the second part, we present RNA splicing regulations under hypoxic conditions, which are mediated by splicing factors and their kinases. This work summarizes and discusses the emerging studies of those two gene expression machineries under hypoxic conditions. Full article
Show Figures

Figure 1

18 pages, 1276 KiB  
Review
Circular RNAs in Muscle Function and Disease
by Simona Greco, Beatrice Cardinali, Germana Falcone and Fabio Martelli
Int. J. Mol. Sci. 2018, 19(11), 3454; https://doi.org/10.3390/ijms19113454 - 3 Nov 2018
Cited by 63 | Viewed by 5180
Abstract
Circular RNAs (circRNAs) are a class of RNA produced during pre-mRNA splicing that are emerging as new members of the gene regulatory network. In addition to being spliced in a linear fashion, exons of pre-mRNAs can be circularized by use of the 3′ [...] Read more.
Circular RNAs (circRNAs) are a class of RNA produced during pre-mRNA splicing that are emerging as new members of the gene regulatory network. In addition to being spliced in a linear fashion, exons of pre-mRNAs can be circularized by use of the 3′ acceptor splice site of upstream exons, leading to the formation of circular RNA species. In this way, genetic information can be re-organized, increasing gene expression potential. Expression of circRNAs is developmentally regulated, tissue and cell-type specific, and shared across eukaryotes. The importance of circRNAs in gene regulation is now beginning to be recognized and some putative functions have been assigned to them, such as the sequestration of microRNAs or proteins, the modulation of transcription, the interference with splicing, and translation of small proteins. In accordance with an important role in normal cell biology, circRNA deregulation has been reported to be associated with diseases. Recent evidence demonstrated that circRNAs are highly expressed in striated muscle tissue, both skeletal and cardiac, that is also one of the body tissue showing the highest levels of alternative splicing. Moreover, initial studies revealed altered circRNA expression in diseases involving striated muscle, suggesting important functions of these molecules in the pathogenetic mechanisms of both heart and skeletal muscle diseases. The recent findings in this field will be described and discussed. Full article
Show Figures

Figure 1

Back to TopTop