microRNAs in action: biogenesis, function and regulation
Open accessAbstract
Ever since microRNAs (miRNAs) were first recognized as an extensive gene family >20 years ago, a broad community of researchers was drawn to investigate the universe of small regulatory RNAs. Although core features of miRNA biogenesis and function were revealed early on, recent years continue to uncover fundamental information on the structural and molecular dynamics of core miRNA machinery, how miRNA substrates and targets are selected from the transcriptome, new avenues for multilevel regulation of miRNA biogenesis and mechanisms for miRNA turnover. Many of these latest insights were enabled by recent technological advances, including massively parallel assays, cryogenic electron microscopy, single-molecule imaging and CRISPR-Cas9 screening. Here, we summarize the current understanding of miRNA biogenesis, function and regulation, and outline challenges to address in the future.
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The canonical microRNA biogenesis pathway involves two sequential processing events catalyzed by RNase III enzymes: Drosha/DGCR8 cleaves primary microRNA transcripts to produce precursor microRNAs, which are exported to the cytoplasm where Dicer processes them into mature microRNAs.
“The canonical microRNA biogenesis pathway involves two sequential processing events catalyzed by RNase III enzymes. In the nucleus, the microprocessor complex involving Drosha/DGCR8 cleaves primary microRNA transcripts (pri-miRs) to produce precursor microRNAs (pre-miRs), which are exported to the cytoplasm, where Dicer processes them into mature microRNAs that are eventually loaded into the RNA-”
From ESRP2–microRNA-122 axis promotes the postnatal onset of liver polyploidization and maturation (2025) · cites this paper as Shang et al. 2023
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Effects of Combinations of Untranslated-Region Sequences on Translation of mRNA
Kirshina, A., Vasileva, O., Kunyk, D., Seregina, K., Muslimov, A., Ivanov, R., & Reshetnikov, V. (2023) · Biomolecules · doi:10.3390/biom13111677 · Cited by 26 · see citing works
ESRP2–microRNA-122 axis promotes the postnatal onset of liver polyploidization and maturation
Bangru, S., Chen, J., Baker, N., Das, D., Chembazhi, U. V., Derham, J. M., Chorghade, S., Arif, W., Alencastro, F., Duncan, A. W., et al. (2025) · Genes & Development · doi:10.1101/gad.352129.124 · Cited by 4 · see citing works
Murphy, R., Villegas-Salmerón, J., Sanz-Rodriguez, A., Engel, T., Mooney, C., Henshall, D. C., & Jimenez-Mateos, E. M. (2025) · PLOS One · doi:10.1371/journal.pone.0326401 · Cited by 3 · see citing works
- Authors
- Shang, R., Lee, S., Senavirathne, G., & Lai, E. C.
- Affiliations
- Memorial Sloan Kettering Cancer Center (US)
- Corresponding author
- Lai, Eric C.
- Venue
- Nature Reviews Genetics
- Published
- 2023-06-28
- Volume
- 24
- Issue
- 12
- Pages
- 816-833
- ISSN
- 1471-0056 (ISSN-L)
- 1471-0064
- PMC
- PMC11087887
- OpenAlex
- W4382400397
- Cited by
- 897
- References
- 6
- Citations by year
- 2026: 241 · 2025: 396 · 2024: 233 · 2023: 27
- FWCI
- 28.50
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Licence
- Locations
- Nature Reviews Genetics (publishedVersion)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion)
- Funders
- New York State Stem Cell Science (C32559GG)
- National Institutes of Health (CA008748, R01-GM083300, 2r01gm083300-18)
- National Cancer Institute (P30CA008748)
- National Institute of General Medical Sciences (R01-GM083300)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cancer Research › MicroRNA in disease regulation
- Life Sciences › Agricultural and Biological Sciences › Plant Science › Plant Molecular Biology Research
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › RNA Research and Splicing
- Keywords
- microRNA, microRNA biogenesis, microRNA function, microRNA regulation, small regulatory RNAs, microRNA processing, CRISPR-Cas9 screen, cryo-electron microscopy, single-molecule imaging
- MeSH terms
- MicroRNAs, Transcriptome
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