Dicer recognizes the 5′ end of RNA for efficient and accurate processing Journal Article
| Authors: | Park, J. E.; Heo, I.; Tian, Y.; Simanshu, D. K.; Chang, H.; Jee, D.; Patel, D. J.; Kim, V. N. |
| Article Title: | Dicer recognizes the 5′ end of RNA for efficient and accurate processing |
| Abstract: | 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. © 2011 Macmillan Publishers Limited. All rights reserved. |
| Journal Title: | Nature |
| Volume: | 475 |
| Issue: | 7355 |
| ISSN: | 0028-0836 |
| Publisher: | Nature Publishing Group |
| Date Published: | 2011-07-14 |
| Start Page: | 201 |
| End Page: | 205 |
| Language: | English |
| DOI: | 10.1038/nature10198 |
| PROVIDER: | scopus |
| PUBMED: | 21753850 |
| PMCID: | PMC4693635 |
| DOI/URL: | |
| Notes: | --- - "Export Date: 17 August 2011" - "CODEN: NATUA" - "Source: Scopus" |
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