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Role of the proline-rich disordered domain of DROSHA in intronic microRNA processing

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Title
Role of the proline-rich disordered domain of DROSHA in intronic microRNA processing
Author(s)
Soomin Son; Baekgyu Kim; Jihye Yang; V Narry Kim
Publication Date
2023-05
Journal
Genes and Development, v.37, no.9-10, pp.383 - 397
Publisher
Cold Spring Harbor Laboratory Press
Abstract
DROSHA serves as a gatekeeper of the microRNA (miRNA) pathway by processing primary transcripts (pri-miRNAs). While the functions of structured domains of DROSHA have been well documented, the contribution of N-terminal proline-rich disordered domain (PRD) remains elusive. Here we show that the PRD promotes the processing of miRNA hairpins located within introns. We identified a DROSHA isoform (p140) lacking the PRD, which is produced by proteolytic cleavage. Small RNA sequencing revealed that p140 is significantly impaired in the maturation of intronic miRNAs. Consistently, our minigene constructs demonstrated that PRD enhances the processing of intronic hairpins, but not those in exons. Splice site mutations did not affect the PRD's enhancing effect on intronic constructs, suggesting that the PRD acts independently of splicing reaction by interacting with sequences residing within introns. The N-terminal regions from zebrafish and Xenopus DROSHA can replace the human counterpart, indicating functional conservation despite poor sequence alignment. Moreover, we found that rapidly evolving intronic miRNAs are generally more dependent on PRD than conserved ones, suggesting a role of PRD in miRNA evolution. Our study reveals a new layer of miRNA regulation mediated by a low-complexity disordered domain that senses the genomic contexts of miRNA loci. © 2023 Son et al.; Published by Cold Spring Harbor Laboratory Press.
URI
https://pr.ibs.re.kr/handle/8788114/13624
DOI
10.1101/gad.350275.122
ISSN
0890-9369
Appears in Collections:
Center for RNA Research(RNA 연구단) > 1. Journal Papers (저널논문)
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