An Endogenous Cluster of Target-directed MicroRNA Degradation Sites Induces Decay of Distinct MicroRNA Families

Overview

Journal bioRxiv

Date 2024 Dec 23

PMID 39713366

Authors

Nicholas M Hiers

Lu Li

Tianqi Li

Peike Sheng

Yuzhi Wang

Conner M Traugot

Michael Yao

Mingyi Xie

Affiliations

Soon will be listed here.

Abstract

While much is known about miRNA biogenesis and canonical miRNA targeting, relatively less is understood about miRNA decay. The major miRNA decay pathway in metazoans is mediated through target-directed miRNA degradation (TDMD), in which certain RNAs can "trigger" miRNA decay. All known triggers for TDMD base pair with the miRNA seed, and extensively base pair on the miRNA 3' end, a pattern that supposedly induces a TDMD-competent conformational change of Argonaute (Ago), allowing for miRNA turnover. Here, we utilized Ago1-CLASH to find that the transcript contains at least two triggers, a "trigger cluster", against miR-9b and the miR-279 family. One of these triggers contains minimal/non-canonical 3' end base pairing but is still sufficient to induce TDMD of the entire miR-279 family. We found that these clustered triggers likely lack cooperativity, the minimal 3' pairing is required for miR-279 family turnover, and probed the in-cell RNA structure of the trigger cluster. Overall, this study expands the list of endogenous triggers and the unexpectedly complex regulatory network governing miRNA degradation.

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