Mechanisms of action of intranuclear microRNAs. Part 2. MicroRNA-mediated regulation of ncRNA transcriptome and alternative splicing




microRNA, miRNA, miR, transcriptome, alternative splicing, spliceosome, review


The scientific review presents the mechanisms of action of intranuclear miRNAs, namely microRNA-mediated regulation of the non-coding RNA (ncRNA) transcriptome and alternative splicing. To write the article, information was searched using Scopus, Web of Science, MedLine, PubMed, Google Scholar, EMBASE, Global Health, The Cochrane Library, CyberLeninka databases. It is emphasized that a significant effect on the composition of the transcriptome is provided by microRNAs in the RNA-induced silencing complex that induce posttranscriptional degradation of long ncRNAs localized in the cell nucleus. Scientists believe that long ncRNAs are involved in the epigenetic regulation of gene silencing through chromatin remodeling. It is shown that long ncRNAs are actively involved in the development of some liver diseases. It is reported that the most important mechanism for expanding the spectrum of the transcriptome in the cell is the alternative splicing of pre-mRNA. The authors present the results of scientific studies that show that pre-mRNA of more than 90 % of human genes are subjected to alternative splicing. It is presented that splicing is performed by a specialized macromolecular formation — suprasplicesome, which is a megacomplex (21 MDA) of nuclear ribonucleroprotein. It is shown that scientists have proposed two models of epigenetic regulation of splicing: kinetic and recruitment one. The authors reveal the main provisions of these models. MicroRNAs are actively involved in splicing. Liver disease may be based on a deficiency of splicing factors and deregulation of alternative splicing caused by the action of miRNAs. Disorders of alternative splicing, which stimulate proliferation, prevent apoptosis and support cell transformation, are a pathognomonic phenomenon in malignant tumors. Thus, the constituent mechanisms of action of intranuclear miRNAs are alteration of the ncRNAs transcriptome and participation in the regulation of alternative splicing. MicroRNA-mediated regulation of the stability of long ncRNAs causes a change in the spectrum of activity of expression of epigenetically regulated genes. Long ncRNAs are actively involved in the development of some liver diseases. Alternative splicing is an integral part of cell differentiation and contributes to the formation of tissue specificity. Alternative splicing and generation of various isoforms of proteins determine molecular consequences that cause the deve­lopment of various pathological conditions.


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Dymshits GM, Sablina OV. Gaped genes and splicing. Vavilov Journal of Genetics and Breeding. 2014;18(1):71-80. (in Russian).

Stcherbic VV, Buchatsky LP. Group of alternatives and splicing phenomenon. Problems of ecological and medical genetics and clinical immunology.2013;(115):30-38. (in Russian).

Alló M, Agirre E, Bessonov S, et al. Argonaute-1 binds transcriptional enhancers and controls constitutive and alternative splicing in human cells. Proc Natl Acad Sci U S A. 2014 Nov 4;111(44):15622-15629. doi:10.1073/pnas.1416858111.

Alló M, Buggiano V, Fededa JP, et al. Control of alternative splicing through siRNA-mediated transcriptional gene silencing. Nat Struct Mol Biol. 2009 Jul;16(7):717-724. doi:10.1038/nsmb.1620.

Broughton JP, Pasquinelli AE. A tale of two sequences: microRNA-target chimeric reads. Genet Sel Evol. 2016 Apr 4;48:31. doi:10.1186/s12711-016-0209-x.

Carithers LJ, Ardlie K, Barcus M, et al. A Novel Approach to High-Quality Postmortem Tissue Procurement: The GTEx Project. Biopreserv Biobank. 2015 Oct;13(5):311-319. doi:10.1089/bio.2015.0032.

Chen K, Dai X, Wu J. Alternative splicing: an important mechanism in stem cell biology. World J Stem Cells. 2015 Jan 26;7(1):1-10. doi:10.4252/wjsc.v7.i1.1.

Cheng Y, Luo C, Wu W, Xie Z, Fu X, Feng Y. Liver-Specific Deletion of SRSF2 Caused Acute Liver Failure and Early Death in Mice. Mol Cell Biol. 2016 May 16;36(11):1628-1638. doi:10.1128/MCB.01071-15.

Fu XD, Ares M Jr. Context-dependent control of alternative splicing by RNA-binding proteins. Nat Rev Genet. 2014 Oct;15(10):689-701. doi:10.1038/nrg3778.

Grossi I, Salvi A, Abeni E, Marchina E, De Petro G. Biological Function of MicroRNA193a-3p in Health and Disease. Int J Genomics. 2017;2017:5913195. doi:10.1155/2017/5913195.

Gunewardena SS, Yoo B, Peng L, et al. Deciphering the Developmental Dynamics of the Mouse Liver Transcriptome. PLoS One. 2015 Oct 23;10(10):e0141220. doi:10.1371/journal.pone.0141220.

He Y, Wu YT, Huang C, et al. Inhibitory effects of long noncoding RNA MEG3 on hepatic stellate cells activation and liver fibrogenesis. Biochim Biophys Acta. 2014 Nov;1842(11):2204-2215. doi:10.1016/j.bbadis.2014.08.015.

Iannone C, Valcárcel J. Chromatin's thread to alternative splicing regulation. Chromosoma. 2013 Dec;122(6):465-474. doi:10.1007/s00412-013-0425-x.

Kalantari R, Chiang CM, Corey DR. Regulation of mammalian transcription and splicing by Nuclear RNAi. Nucleic Acids Res. 2016 Jan 29;44(2):524-537. doi:10.1093/nar/gkv1305.

Kucherenko MM, Shcherbata HR. miRNA targeting and alternative splicing in the stress response - events hosted by membrane-less compartments. J Cell Sci. 2018 Feb 14;131(4):jcs202002. doi:10.1242/jcs.202002.

Li Y, Ren M, Zhao Y, et al. MicroRNA-26a inhibits proliferation and metastasis of human hepatocellular carcinoma by regulating DNMT3B-MEG3 axis. Oncol Rep. 2017 Jun;37(6):3527-3535. doi:10.3892/or.2017.5579.

Liu Y, Ren F, Luo Y, Rong M, Chen G, Dang Y. Down-Regulation of MiR-193a-3p Dictates Deterioration of HCC: A Clinical Real-Time qRT-PCR Study. Med Sci Monit. 2015 Aug 11;21:2352-2360. doi:10.12659/MSM.894077.

Liu Y, Liu X, Lin C, et al. Noncoding RNAs regulate alternative splicing in Cancer. J Exp Clin Cancer Res. 2021 Jan 6;40(1):11. doi:10.1186/s13046-020-01798-2.

Ma K, He Y, Zhang H, et al. DNA methylation-regulated miR-193a-3p dictates resistance of hepatocellular carcinoma to 5-fluorouracil via repression of SRSF2 expression. J Biol Chem. 2012 Feb 17;287(8):5639-5649. doi:10.1074/jbc.M111.291229.

Moehle EA, Braberg H, Krogan NJ, Guthrie C. Adventures in time and space: splicing efficiency and RNA polymerase II elongation rate. RNA Biol. 2014;11(4):313-319. doi:10.4161/rna.28646.

Pan Q, Shai O, Lee LJ, Frey BJ, Blencowe BJ. Deep surveying of alternative splicing complexity in the human transcriptome by high-throughput sequencing. Nat Genet. 2008 Dec;40(12):1413-1415. doi:10.1038/ng.259.

Peng L, Yoo B, Gunewardena SS, Lu H, Klaassen CD, Zhong XB. RNA sequencing reveals dynamic changes of mRNA abundance of cytochromes P450 and their alternative transcripts during mouse liver development. Drug Metab Dispos. 2012 Jun;40(6):1198-209. doi:10.1124/dmd.112.045088.

Pihlajamäki J, Lerin C, Itkonen P, et al. Expression of the splicing factor gene SFRS10 is reduced in human obesity and contributes to enhanced lipogenesis. Cell Metab. 2011 Aug 3;14(2):208-218. doi:10.1016/j.cmet.2011.06.007.

Pu M, Chen J, Tao Z, et al. Regulatory network of miRNA on its target: coordination between transcriptional and post-transcriptional regulation of gene expression. Cell Mol Life Sci. 2019 Feb;76(3):441-451. doi:10.1007/s00018-018-2940-7.

Saldi T, Cortazar MA, Sheridan RM, Bentley DL. Coupling of RNA Polymerase II Transcription Elongation with Pre-mRNA Splicing. J Mol Biol. 2016 Jun 19;428(12):2623-2635. doi:10.1016/j.jmb.2016.04.017.

Shefer K, Sperling J, Sperling R. The Supraspliceosome - A Multi-Task Machine for Regulated Pre-mRNA Processing in the Cell Nucleus. Comput Struct Biotechnol J. 2014 Sep 28;11(19):113-122. doi:10.1016/j.csbj.2014.09.008.

Sokół E, Kędzierska H, Czubaty A, et al. microRNA-mediated regulation of splicing factors SRSF1, SRSF2 and hnRNP A1 in context of their alternatively spliced 3'UTRs. Exp Cell Res. 2018 Feb 15;363(2):208-217. doi:10.1016/j.yexcr.2018.01.009.

Tremblay MP, Armero VE, Allaire A, et al. Global profiling of alternative RNA splicing events provides insights into molecular differences between various types of hepatocellular carcinoma. BMC Genomics. 2016 Aug 26;17(1):683. doi:10.1186/s12864-016-3029-z.

Ulitsky I. Interactions between short and long noncoding RNAs. FEBS Lett. 2018 Sep;592(17):2874-2883. doi:10.1002/1873-3468.13085.

Urbanski LM, Leclair N, Anczuków O. Alternative-splicing defects in cancer: Splicing regulators and their downstream targets, guiding the way to novel cancer therapeutics. Wiley Interdiscip Rev RNA. 2018 Jul;9(4):e1476. doi:10.1002/wrna.1476.

Wang ET, Sandberg R, Luo S, et al. Alternative isoform regulation in human tissue transcriptomes. Nature. 2008 Nov 27;456(7221):470-476. doi:10.1038/nature07509.

Wang X, Wang J. High-content hydrogen water-induced downregulation of miR-136 alleviates non-alcoholic fatty liver disease by regulating Nrf2 via targeting MEG3. Biol Chem. 2018 Mar 28;399(4):397-406. doi:10.1515/hsz-2017-0303.

Webster MW, Stowell JAW, Tang TTL, Passmore LA. Analysis of mRNA deadenylation by multi-protein complexes. Methods. 2017 Aug 15;126:95-104. doi:10.1016/j.ymeth.2017.06.009.

Yang JJ, Tao H, Deng ZY, Lu C, Li J. Non-coding RNA-mediated epigenetic regulation of liver fibrosis. Metabolism. 2015 Nov;64(11):1386-1394. doi:10.1016/j.metabol.2015.08.004.

Yeo G, Holste D, Kreiman G, Burge CB. Variation in alternative splicing across human tissues. Genome Biol. 2004;5(10):R74. doi:10.1186/gb-2004-5-10-r74.

Zhao T, Xu J, Liu L, et al. Computational identification of epigenetically regulated lncRNAs and their associated genes based on integrating genomic data. FEBS Lett. 2015 Feb 13;589(4):521-531. doi:10.1016/j.febslet.2015.01.013.



How to Cite

Abaturov, A., & Babуch V. (2022). Mechanisms of action of intranuclear microRNAs. Part 2. MicroRNA-mediated regulation of ncRNA transcriptome and alternative splicing. CHILD`S HEALTH, 17(1), 48–53.



Theoretical Medicine

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