AI Article Synopsis
- The study highlights the importance of DICER in accurately cleaving shRNAs and pre-miRNAs for effective gene silencing.
- Researchers conducted extensive DICER assays on over 20,000 shRNAs and identified a beneficial 22-bulge that enhances DICER's cleavage efficiency and gene-silencing capability.
- The findings reveal how variations in single-nucleotide bulges influence DICER's cleavage sites and miRNA functions, contributing to better understanding and potential improvements in shRNA design for gene regulation.
Article Abstract
The accurate and efficient cleavage of shRNAs and pre-miRNAs by DICER is crucial for their gene-silencing activity. Here, we conduct high-throughput DICER cleavage assays for more than ~20,000 different shRNAs and show the comprehensive cleavage activities of DICER on these sequences. We discover a single-nucleotide bulge (22-bulge), which facilitates the cleavage activity of DICER on shRNAs and human pre-miRNAs. As a result, this 22-bulge enhances the gene-silencing activity of shRNAs and the accuracy of miRNA biogenesis. In addition, various single-nucleotide polymorphism-edited 22-bulges are found to govern the cleavage sites of DICER on pre-miRNAs and thereby control their functions. Finally, we identify the single cleavage of DICER and reveal its molecular mechanism. Our findings improve the understanding of the DICER cleavage mechanism, provide a foundation for the design of accurate and efficient shRNAs for gene-silencing, and indicate the function of bulges in regulating miRNA biogenesis.
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Source |
|---|---|
| http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9018771 | PMC |
| http://dx.doi.org/10.1038/s41467-022-29822-3 | DOI Listing |
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