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3’ Uridylation Expands miRNA Target Repertoire

ABSTRACT: Many microRNAs (miRNAs) exist alongside abundant miRNA isoforms (isomiRs), most of which arise from post-maturation sequence modifications, such as 3’ uridylation. However, the ways in which these sequence modifications affect miRNA function remain poorly understood. Here, using human miR-27a in cell lines as a model, we have discovered that a nonfunctional target site unable to base pair extensively with the miRNA seed sequence can regain function when an upstream adenosine is able to base-pair with a post-transcriptionally added uridine in the miR-27a tail. This Tail-U-Mediated Repression (TUMR) is abolished in cells lacking the uridylation enzymes TUT4 and TUT7, indicating that uridylation alters miRNA function by modulating target recognition. We identified a set of non-canonical targets in human cells that are specifically regulated by uridylated miR-27a. We provide evidence that TUMR expands the targets of other endogenous miRNAs. Our study reveals a function for uridylated isomiRs in regulating non-canonical miRNA targets.

ORGANISM(S): Homo sapiens

PROVIDER: GSE121327 | GEO | 2019/08/15

REPOSITORIES: GEO

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