Functional parameters of Dicer-independent microRNA biogenesis Journal Article
| Authors: | Yang, J. S.; Maurin, T.; Lai, E. C. |
| Article Title: | Functional parameters of Dicer-independent microRNA biogenesis |
| Abstract: | Until recently, a Dicer-class RNase III enzyme was believed to be essential for microRNA (miRNA) biogenesis in all animals. The conserved vertebrate locus mir-451 defies this expectation and instead matures by direct cleavage of its pre-miRNA hairpin via the Slicer activity of Argonaute2 (Ago2). In this study, we used structure-function analysis to define the functional parameters of Ago2-mediated miRNA biogenesis. These include (1) the requirement for base-pairing at most, but not all, positions within the pre-mir-451 stem; (2) surprisingly little influence of the 5′-nucleotide on Ago sorting; (3) substantial influence of Ago protein stoichiometry on mir-451 maturation; (4) strong influence of G:C content in the distal stem on 3′ resection of cleaved mir-451 substrates; and (5) the influence of hairpin length on substrate utilization by Ago2 and Dicer. Unexpectedly, we find that certain hairpin lengths confer competence to mature via both Dicer-mediated and Ago2-mediated pathways, and we show, in fact, that a conventional shRNA can traverse the Dicer-independent pathway. Altogether, these data inform the design of effective Dicer-independent substrates for gene silencing and reveal novel aspects of substrate handling by Ago proteins. Published by Cold Spring Harbor Laboratory Press. Copyright © 2012 RNA Society. |
| Keywords: | microrna; dicer; ago2 |
| Journal Title: | RNA |
| Volume: | 18 |
| Issue: | 5 |
| ISSN: | 1355-8382 |
| Publisher: | Cold Spring Harbor Laboratory Press |
| Date Published: | 2012-05-01 |
| Start Page: | 945 |
| End Page: | 957 |
| Language: | English |
| DOI: | 10.1261/rna.032938.112 |
| PROVIDER: | scopus |
| PMCID: | PMC3334703 |
| PUBMED: | 22461413 |
| DOI/URL: | |
| Notes: | --- - "Export Date: 1 May 2012" - "CODEN: RNARF" - "Source: Scopus" |
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