Genomic Clustering Facilitates Nuclear Processing of Suboptimal Pri-miRNA Loci

Overview

Journal Mol Cell

Publisher Cell Press

Specialty Cell Biology

Date 2020 Apr 18

PMID 32302542

Citations 24

Authors

Renfu Shang

S Chan Baek

Kijun Kim

Boseon Kim

V Narry Kim

Eric C Lai

Affiliations

Soon will be listed here.

Abstract

Nuclear processing of most miRNAs is mediated by Microprocessor, comprised of RNase III enzyme Drosha and its cofactor DGCR8. Here, we uncover a hidden layer of Microprocessor regulation via studies of Dicer-independent mir-451, which is clustered with canonical mir-144. Although mir-451 is fully dependent on Drosha/DGCR8, its short stem and small terminal loop render it an intrinsically weak Microprocessor substrate. Thus, it must reside within a cluster for normal biogenesis, although the identity and orientation of its neighbor are flexible. We use DGCR8 tethering assays and operon structure-function assays to demonstrate that local recruitment and transfer of Microprocessor enhances suboptimal substrate processing. This principle applies more broadly since genomic analysis indicates suboptimal canonical miRNAs are enriched in operons, and we validate several of these experimentally. Proximity-based enhancement of suboptimal hairpin processing provides a rationale for genomic retention of certain miRNA operons and may explain preferential evolutionary emergence of miRNA operons.

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