The DOI matches its Crossref record; 7 of the 7 references it cites were found in a registry or an index.
Dicer recognizes the 5′ end of RNA for efficient and accurate processing
Open accessAbstract
A hallmark of RNA silencing is a class of approximately 22-nucleotide RNAs that are processed from double-stranded RNA precursors by Dicer. Accurate processing by Dicer is crucial for the functionality of microRNAs (miRNAs). The current model posits that Dicer selects cleavage sites by measuring a set distance from the 3′ overhang of the double-stranded RNA terminus. Here we report that human Dicer anchors not only the 3′ end but also the 5′ end, with the cleavage site determined mainly by the distance (∼22 nucleotides) from the 5′ end (5′ counting rule). This cleavage requires a 5′-terminal phosphate group. Further, we identify a novel basic motif (5′ pocket) in human Dicer that recognizes the 5′-phosphorylated end. The 5′ counting rule and the 5′ anchoring residues are conserved in Drosophila Dicer-1, but not in Giardia Dicer. Mutations in the 5′ pocket reduce processing efficiency and alter cleavage sites in vitro. Consistently, miRNA biogenesis is perturbed in vivo when Dicer-null embryonic stem cells are replenished with the 5′-pocket mutant. Thus, 5′-end recognition by Dicer is important for precise and effective biogenesis of miRNAs. Insights from this study should also afford practical benefits to the design of small hairpin RNAs.
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Cites
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miRNPs: a novel class of ribonucleoproteins containing numerous microRNAs
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Cited by
Regulation of microRNA biogenesis
Ha, M., & Kim, V. N. (2014) · Nature Reviews Molecular Cell Biology · doi:10.1038/nrm3838 · Cited by 5,462
Self-citationBartel, D. P. (2018) · Cell · doi:10.1016/j.cell.2018.03.006 · Cited by 3,751
microRNAs in action: biogenesis, function and regulation
Shang, R., Lee, S., Senavirathne, G., & Lai, E. C. (2023) · Nature Reviews Genetics · doi:10.1038/s41576-023-00611-y · Cited by 897
IsomiRs – the overlooked repertoire in the dynamic microRNAome
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Beyond Secondary Structure: Primary-Sequence Determinants License Pri-miRNA Hairpins for Processing
Auyeung, V. C., Ulitsky, I., McGeary, S. E., & Bartel, D. P. (2013) · Cell · doi:10.1016/j.cell.2013.01.031 · Cited by 434
Metadata
- Authors
- Park, J.-E., Heo, I., Tian, Y., Simanshu, D. K., Chang, H., Jee, D., Patel, D. J., & Kim, V. N.
- Venue
- Nature
- Published
- 2011-07
- Volume
- 475
- Issue
- 7355
- Pages
- 201-205
- ISSN
- 0028-0836 (ISSN-L)
- 1476-4687
- OpenAlex
- W1991737083
- Cited by
- 512
- References
- 7
- FWCI
- 14.69
- Type
- journal article
- Language
- en
- Open access
- green
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