MicroRNA Biogenesis: Regulating the Regulators

Overview

Journal Crit Rev Biochem Mol Biol

Publisher Informa Healthcare

Specialties Biochemistry
Molecular Biology

Date 2012 Nov 21

PMID 23163351

Citations 150

Authors

Emily F Finnegan

Amy E Pasquinelli

Affiliations

Soon will be listed here.

Abstract

MicroRNAs (miRNAs) function as 21-24 nucleotide guide RNAs that use partial base-pairing to recognize target messenger RNAs and repress their expression. As a large fraction of protein-coding genes are under miRNA control, production of the appropriate level of specific miRNAs at the right time and in the right place is integral to most gene regulatory pathways. MiRNA biogenesis initiates with transcription, followed by multiple processing steps to produce the mature miRNA. Every step of miRNA production is subject to regulation and disruption of these control mechanisms has been linked to numerous human diseases, where the balance between the expression of miRNAs and their targets becomes distorted. Here we review the basic steps of miRNA biogenesis and describe the various factors that control miRNA transcription, processing, and stability in animal cells. The tremendous effort put into producing the appropriate type and level of specific miRNAs underscores the critical role of these small RNAs in gene regulation.

Citing Articles

hsa-miR-548d-3p: a potential microRNA to target nucleocapsid and/or capsid genes in multiple members of the Flaviviridae family.

Cayatineto H, Hakim S Front Bioinform. 2025; 4:1487292.

PMID: 39877236 PMC: 11772435. DOI: 10.3389/fbinf.2024.1487292.

A genome-wide association study identifies genetic variants associated with hip pain in the UK Biobank cohort (N = 221,127).

Pan Q, Tao Y, Cai T, Veluchamy A, Hebert H, Zhu P Sci Rep. 2025; 15(1):2812.

PMID: 39843573 PMC: 11754597. DOI: 10.1038/s41598-025-85871-w.

Dual Roles of microRNA-122 in Hepatocellular Carcinoma and Breast Cancer Progression and Metastasis: A Comprehensive Review.

Al Ageeli E Curr Issues Mol Biol. 2024; 46(11):11975-11992.

PMID: 39590305 PMC: 11592835. DOI: 10.3390/cimb46110711.

Benchmarking the negatives: Effect of negative data generation on the classification of miRNA-mRNA interactions.

Cohen-Davidi E, Veksler-Lublinsky I PLoS Comput Biol. 2024; 20(8):e1012385.

PMID: 39186797 PMC: 11379385. DOI: 10.1371/journal.pcbi.1012385.

Global progress and future prospects of early gastric cancer screening.

Huang Y, Shao Y, Yu X, Chen C, Guo J, Ye G J Cancer. 2024; 15(10):3045-3064.

PMID: 38706913 PMC: 11064266. DOI: 10.7150/jca.95311.

References

Borchert G, Lanier W, Davidson B . RNA polymerase III transcribes human microRNAs. Nat Struct Mol Biol. 2006; 13(12):1097-101. DOI: 10.1038/nsmb1167. View

Warf M, Shepherd B, Johnson W, Bass B . Effects of ADARs on small RNA processing pathways in C. elegans. Genome Res. 2012; 22(8):1488-98. PMC: 3409262. DOI: 10.1101/gr.134841.111. View

Roush S, Slack F . The let-7 family of microRNAs. Trends Cell Biol. 2008; 18(10):505-16. DOI: 10.1016/j.tcb.2008.07.007. View

Viswanathan S, Powers J, Einhorn W, Hoshida Y, Ng T, Toffanin S . Lin28 promotes transformation and is associated with advanced human malignancies. Nat Genet. 2009; 41(7):843-8. PMC: 2757943. DOI: 10.1038/ng.392. View

Pasquinelli A . MicroRNAs and their targets: recognition, regulation and an emerging reciprocal relationship. Nat Rev Genet. 2012; 13(4):271-82. DOI: 10.1038/nrg3162. View

Thomson J, Newman M, Parker J, Morin-Kensicki E, Wright T, Hammond S . Extensive post-transcriptional regulation of microRNAs and its implications for cancer. Genes Dev. 2006; 20(16):2202-7. PMC: 1553203. DOI: 10.1101/gad.1444406. View

Wagner R, Smith J, Cooperman B, Nishikura K . A double-stranded RNA unwinding activity introduces structural alterations by means of adenosine to inosine conversions in mammalian cells and Xenopus eggs. Proc Natl Acad Sci U S A. 1989; 86(8):2647-51. PMC: 286974. DOI: 10.1073/pnas.86.8.2647. View

Nam Y, Chen C, Gregory R, Chou J, Sliz P . Molecular basis for interaction of let-7 microRNAs with Lin28. Cell. 2011; 147(5):1080-91. PMC: 3277843. DOI: 10.1016/j.cell.2011.10.020. View

Kato M, Putta S, Wang M, Yuan H, Lanting L, Nair I . TGF-beta activates Akt kinase through a microRNA-dependent amplifying circuit targeting PTEN. Nat Cell Biol. 2009; 11(7):881-9. PMC: 2744130. DOI: 10.1038/ncb1897. View

10.

Viswanathan S, Daley G, Gregory R . Selective blockade of microRNA processing by Lin28. Science. 2008; 320(5872):97-100. PMC: 3368499. DOI: 10.1126/science.1154040. View

11.

Bernstein E, Caudy A, Hammond S, Hannon G . Role for a bidentate ribonuclease in the initiation step of RNA interference. Nature. 2001; 409(6818):363-6. DOI: 10.1038/35053110. View

12.

Lee Y, Jeon K, Lee J, Kim S, Kim V . MicroRNA maturation: stepwise processing and subcellular localization. EMBO J. 2002; 21(17):4663-70. PMC: 126204. DOI: 10.1093/emboj/cdf476. View

13.

Massague J, Seoane J, Wotton D . Smad transcription factors. Genes Dev. 2005; 19(23):2783-810. DOI: 10.1101/gad.1350705. View

14.

Yang W, Chendrimada T, Wang Q, Higuchi M, Seeburg P, Shiekhattar R . Modulation of microRNA processing and expression through RNA editing by ADAR deaminases. Nat Struct Mol Biol. 2005; 13(1):13-21. PMC: 2950615. DOI: 10.1038/nsmb1041. View

15.

Macias S, Plass M, Stajuda A, Michlewski G, Eyras E, Caceres J . DGCR8 HITS-CLIP reveals novel functions for the Microprocessor. Nat Struct Mol Biol. 2012; 19(8):760-6. PMC: 3442229. DOI: 10.1038/nsmb.2344. View

16.

Kim V, Han J, Siomi M . Biogenesis of small RNAs in animals. Nat Rev Mol Cell Biol. 2009; 10(2):126-39. DOI: 10.1038/nrm2632. View

17.

Kawahara Y, Zinshteyn B, Chendrimada T, Shiekhattar R, Nishikura K . RNA editing of the microRNA-151 precursor blocks cleavage by the Dicer-TRBP complex. EMBO Rep. 2007; 8(8):763-9. PMC: 1978079. DOI: 10.1038/sj.embor.7401011. View

18.

Martin G, Keller W . RNA-specific ribonucleotidyl transferases. RNA. 2007; 13(11):1834-49. PMC: 2040100. DOI: 10.1261/rna.652807. View

19.

Pilotte J, Dupont-Versteegden E, Vanderklish P . Widespread regulation of miRNA biogenesis at the Dicer step by the cold-inducible RNA-binding protein, RBM3. PLoS One. 2011; 6(12):e28446. PMC: 3228759. DOI: 10.1371/journal.pone.0028446. View

20.

Morlando M, Ballarino M, Gromak N, Pagano F, Bozzoni I, Proudfoot N . Primary microRNA transcripts are processed co-transcriptionally. Nat Struct Mol Biol. 2009; 15(9):902-9. PMC: 6952270. DOI: 10.1038/nsmb.1475. View