AI Article Synopsis
- The study identifies a noncanonical cleavage mechanism of the microprocessor complex (MP) that is responsible for processing certain pri-miRNAs, which the traditional model can't fully explain.
- The researchers analyzed a large dataset of pri-miRNA sequences to uncover this new mechanism, which does not require key RNA and protein components needed in the canonical process.
- This noncanonical mechanism is found to be conserved across various animal species and is particularly important in C. elegans, indicating a wider range of RNA substrates that the microprocessor can process, expanding our understanding of miRNA biogenesis.
Article Abstract
Microprocessor (MP), DROSHA-DGCR8, processes primary miRNA transcripts (pri-miRNAs) to initiate miRNA biogenesis. The canonical cleavage mechanism of MP has been extensively investigated and comprehensively validated for two decades. However, this canonical mechanism cannot account for the processing of certain pri-miRNAs in animals. In this study, by conducting high-throughput pri-miRNA cleavage assays for approximately 260,000 pri-miRNA sequences, we discovered and comprehensively characterized a noncanonical cleavage mechanism of MP. This noncanonical mechanism does not need several RNA and protein elements essential for the canonical mechanism; instead, it utilizes previously unrecognized DROSHA dsRNA recognition sites (DRESs). Interestingly, the noncanonical mechanism is conserved across animals and plays a particularly significant role in C. elegans. Our established noncanonical mechanism elucidates MP cleavage in numerous RNA substrates unaccounted for by the canonical mechanism in animals. This study suggests a broader substrate repertoire of animal MPs and an expanded regulatory landscape for miRNA biogenesis.
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| http://dx.doi.org/10.1016/j.molcel.2023.05.004 | DOI Listing |
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