Mechanisms of action of intranuclear microRNAs. Part 1. Influence of microRNA on transcription

Authors

DOI:

https://doi.org/10.22141/2224-0551.16.8.2021.248712

Keywords:

microRNA, miRNA, miR, microRNA-mediated transcriptional silencing, transcription, heterochromatin, Argonaute proteins, review

Abstract

The scientific review presents the mechanisms of action of intranuclear miRNAs, namely the influence of intranuclear miRNAs on transcription. To write the article, information was searched using Scopus, Web of Science, MedLine, PubMed, Google Scholar, EMBASE, Global Health, The Cochrane Library, CyberLeninka databases. The authors cite differences between nuclear and cytoplasmic functions of miRNAs. It is emphasized that the regulation of miRNA transcription is carried out mainly due to the formation of heterochromatin, and the control of translation is performed by various mechanisms. The result of microRNA action in most cases is a decrease in gene expression. However, in some cases, miRNAs can enhance gene expression activity. Intranuclear miRNAs are able to induce pretranslational silencing of protein-encoding genes, activate transcription, alter ncRNA trans­criptome, and participate in the regulation of alternative splicing. It is shown that microRNA-mediated transcriptional silencing is induced by small RNAs in the cell nucleus, which promote DNA methylation and together with Argonaute proteins are involved in chromatin modification. In microRNA-mediated transcriptional silencing, DNA methyltransferases are recruited, RNA-induced transcriptional silencing complex is formed, microRNA interacts with promoter-associated nсRNAs and DNA of target genes, and heterochromatin is formed. The authors state that the formation of heterochromatin occurs in several stages: the initiation of assembly, assembly and distribution of heterochromatin. Thus, miRNAs can act as regulators of various processes and differences between the functions and effects of miRNAs depend on their location in the nucleus or cytoplasm of the cell. MicroRNAs in the cell nucleus control transcription, in the cytoplasm — translation. The mechanism of action of intranuclear miRNAs includes induction of pretranslational silencing of protein-encoding genes, activation of transcription, alteration of ncRNA transcriptomes, participation in the regulation of alternative splicing.

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References

Allshire RC, Madhani HD. Ten principles of heterochromatin formation and function. Nat Rev Mol Cell Biol. 2018 Apr;19(4):229-244. doi:10.1038/nrm.2017.119.

Bayne EH, White SA, Kagansky A, et al. Stc1: a critical link between RNAi and chromatin modification required for heterochromatin integrity. Cell. 2010 Mar 5;140(5):666-677. doi:10.1016/j.cell.2010.01.038.

Benetti R, Gonzalo S, Jaco I, et al. A mammalian microRNA cluster controls DNA methylation and telomere recombination via Rbl2-dependent regulation of DNA methyltransferases. Nat Struct Mol Biol. 2008 Mar;15(3):268-279. doi:10.1038/nsmb.1399.

Catalanotto C, Cogoni C, Zardo G. MicroRNA in Control of Gene Expression: An Overview of Nuclear Functions. Int J Mol Sci. 2016 Oct 13;17(10):1712. doi:10.3390/ijms17101712.

Cheng X, Blumenthal RM. Mammalian DNA methyltransferases: a structural perspective. Structure. 2008 Mar;16(3):341-350. doi:10.1016/j.str.2008.01.004.

Creamer KM, Partridge JF. RITS-connecting transcription, RNA interference, and heterochromatin assembly in fission yeast. Wiley Interdiscip Rev RNA. 2011 Sep-Oct;2(5):632-646. doi:10.1002/wrna.80.

Goto DB, Nakayama J. RNA and epigenetic silencing: insight from fission yeast. Dev Growth Differ. 2012 Jan;54(1):129-141. doi:10.1111/j.1440-169X.2011.01310.x.

Grewal SI, Jia S. Heterochromatin revisited. Nat Rev Genet. 2007 Jan;8(1):35-46. doi:10.1038/nrg2008.

Holoch D, Moazed D. Small-RNA loading licenses Argonaute for assembly into a transcriptional silencing complex. Nat Struct Mol Biol. 2015 Apr;22(4):328-335. doi:10.1038/nsmb.2979.

Khan AW. Nuclear functions of microRNAs relevant to the cardiovascular system. Transl Res. 2021 Apr;230:151-163. doi:10.1016/j.trsl.2020.11.004.

Kim DH, Saetrom P, Snøve O Jr, Rossi JJ. MicroRNA-directed transcriptional gene silencing in mammalian cells. Proc Natl Acad Sci U S A. 2008 Oct 21;105(42):16230-16235. doi:10.1073/pnas.0808830105.

King VM, Borchert GM. MicroRNA Expression: Protein Participants in MicroRNA Regulation. Methods Mol Biol. 2017;1617:27-37. doi:10.1007/978-1-4939-7046-9_2.

Lejeune E, Bayne EH, Allshire RC. On the connection between RNAi and heterochromatin at centromeres. Cold Spring Harb Symp Quant Biol. 2010;75:275-283. doi:10.1101/sqb.2010.75.024.

Li F, Martienssen R, Cande WZ. Coordination of DNA replication and histone modification by the Rik1-Dos2 complex. Nature. 2011 Jul 3;475(7355):244-248. doi:10.1038/nature10161.

Liu H, Lei C, He Q, Pan Z, Xiao D, Tao Y. Nuclear functions of mammalian MicroRNAs in gene regulation, immunity and cancer. Mol Cancer. 2018 Feb 22;17(1):64. doi:10.1186/s12943-018-0765-5.

Matsui M, Chu Y, Zhang H, et al. Promoter RNA links transcriptional regulation of inflammatory pathway genes. Nucleic Acids Res. 2013 Dec;41(22):10086-10109. doi:10.1093/nar/gkt777.

Mazzoccoli L, Robaina MC, Apa AG, et al. MiR-29 silencing modulates the expression of target genes related to proliferation, apoptosis and methylation in Burkitt lymphoma cells. J Cancer Res Clin Oncol. 2018 Mar;144(3):483-497. doi:10.1007/s00432-017-2575-3.

Mohr AM, Mott JL. Overview of microRNA biology. Semin Liver Dis. 2015 Feb;35(1):3-11. doi:10.1055/s-0034-1397344.

Nakama M, Kawakami K, Kajitani T, Urano T, Murakami Y. DNA-RNA hybrid formation mediates RNAi-directed heterochromatin formation. Genes Cells. 2012 Mar;17(3):218-233. doi:10.1111/j.1365-2443.2012.01583.x.

Napoli S. Targeting Promoter-Associated RNAs by siRNAs. Methods Mol Biol. 2017;1543:209-219. doi:10.1007/978-1-4939-6716-2_11.

Place RF, Li LC, Pookot D, Noonan EJ, Dahiya R. MicroRNA-373 induces expression of genes with complementary promoter sequences. Proc Natl Acad Sci U S A. 2008 Feb 5;105(5):1608-1613. doi:10.1073/pnas.0707594105.

Portnoy V, Huang V, Place RF, Li LC. Small RNA and transcriptional upregulation. Wiley Interdiscip Rev RNA. 2011 Sep-Oct;2(5):748-760. doi:10.1002/wrna.90.

Sadakierska-Chudy A. MicroRNAs: Diverse Mechanisms of Action and Their Potential Applications as Cancer Epi-Therapeutics. Biomolecules. 2020 Sep 7;10(9):1285. doi:10.3390/biom10091285.

Schalch T, Job G, Shanker S, Partridge JF, Joshua-Tor L. The Chp1-Tas3 core is a multifunctional platform critical for gene silencing by RITS. Nat Struct Mol Biol. 2011 Nov 13;18(12):1351-1357. doi:10.1038/nsmb.2151.

Shanker S, Job G, George OL, Creamer KM, Shaban A, Partridge JF. Continuous requirement for the Clr4 complex but not RNAi for centromeric heterochromatin assembly in fission yeast harboring a disrupted RITS complex. PLoS Genet. 2010 Oct 28;6(10):e1001174. doi:10.1371/journal.pgen.1001174.

Toscano-Garibay JD, Aquino-Jarquin G. Transcriptional regulation mechanism mediated by miRNA-DNA•DNA triplex structure stabilized by Argonaute. Biochim Biophys Acta. 2014 Nov;1839(11):1079-1083. doi:10.1016/j.bbagrm.2014.07.016.

Verdel A, Jia S, Gerber S, et al. RNAi-mediated targeting of heterochromatin by the RITS complex. Science. 2004 Jan 30;303(5658):672-676. doi:10.1126/science.1093686.

Younger ST, Pertsemlidis A, Corey DR. Predicting potential miRNA target sites within gene promoters. Bioorg Med Chem Lett. 2009 Jul 15;19(14):3791-3794. doi:10.1016/j.bmcl.2009.04.032.

Yu CY, Kuo HC. The emerging roles and functions of circular RNAs and their generation. J Biomed Sci. 2019 Apr 25;26(1):29. doi:10.1186/s12929-019-0523-z.

Published

2022-02-28

How to Cite

Abaturov, A., & Babуch V. (2022). Mechanisms of action of intranuclear microRNAs. Part 1. Influence of microRNA on transcription. CHILD`S HEALTH, 16(8), 546–553. https://doi.org/10.22141/2224-0551.16.8.2021.248712

Issue

Section

Theoretical Medicine

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