Parameters of clustered suboptimal miRNA biogenesis Journal Article
| Authors: | Shang, R.; Lai, E. C. |
| Article Title: | Parameters of clustered suboptimal miRNA biogenesis |
| Abstract: | The nuclear cleavage of a suboptimal primary miRNA hairpin by the Drosha/DGCR8 complex (“Microprocessor”) can be enhanced by an optimal miRNA neighbor, a phenomenon termed cluster assistance. Several features and biological impacts of this new layer of miRNA regulation are not fully known. Here, we elucidate the parameters of cluster assistance of a suboptimal miRNA and also reveal competitive interactions amongst optimal miRNAs within a cluster. We exploit cluster assistance as a functional assay for suboptimal processing and use this to invalidate putative suboptimal substrates, as well as identify a "solo" suboptimal miRNA. Finally, we report complexity in how specific mutations might affect the biogenesis of clustered miRNAs in disease contexts. This includes how an operon context can buffer the effect of a deleterious processing variant, but reciprocally how a point mutation can have a nonautonomous effect to impair the biogenesis of a clustered, suboptimal, neighbor. These data expand our knowledge regarding regulated miRNA biogenesis in humans and represent a functional assay for empirical definition of suboptimal Microprocessor substrates. © 2023 National Academy of Sciences. All rights reserved. |
| Keywords: | protein expression; gene mutation; genetics; nonhuman; metabolism; microrna; gene amplification; gene expression; rna binding protein; rna-binding proteins; cell culture; western blotting; dactinomycin; real time polymerase chain reaction; micrornas; rna processing; rna extraction; biogenesis; ribonuclease iii; rna processing, post-transcriptional; northern blotting; gene knockdown; humans; human; article; luciferase assay; hek293t cell line; crispr associated endonuclease cas9 |
| Journal Title: | Proceedings of the National Academy of Sciences of the United States of America |
| Volume: | 120 |
| Issue: | 41 |
| ISSN: | 0027-8424 |
| Publisher: | National Academy of Sciences |
| Date Published: | 2023-10-10 |
| Start Page: | e2306727120 |
| Language: | English |
| DOI: | 10.1073/pnas.2306727120 |
| PUBMED: | 37788316 |
| PROVIDER: | scopus |
| PMCID: | PMC10576077 |
| DOI/URL: | |
| Notes: | Article -- MSK Cancer Center Support Grant (P30 CA008748) acknowledged in PubMed and PDF -- MSK corresponding author is Eric Lai -- Source: Scopus |
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