MicroRNA turnover: a tale of tailing, trimming, and targets

Trends Biochem Sci. 2023 Jan;48(1):26-39. doi: 10.1016/j.tibs.2022.06.005. Epub 2022 Jul 7.

Abstract

MicroRNAs (miRNAs) post-transcriptionally repress gene expression by guiding Argonaute (AGO) proteins to target mRNAs. While much is known about the regulation of miRNA biogenesis, miRNA degradation pathways are comparatively poorly understood. Although miRNAs generally exhibit slow turnover, they can be rapidly degraded through regulated mechanisms that act in a context- or sequence-specific manner. Recent work has revealed a particularly important role for specialized target interactions in controlling rates of miRNA degradation. Engagement of these targets is associated with the addition and removal of nucleotides from the 3' ends of miRNAs, a process known as tailing and trimming. Here we review these mechanisms of miRNA modification and turnover, highlighting the contexts in which they impact miRNA stability and discussing important questions that remain unanswered.

Keywords: Argonaute; TDMD; ZSWIM8; degradation; miRNA; tailing and trimming; target-directed miRNA degradation.

Publication types

  • Review
  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Argonaute Proteins / genetics
  • Argonaute Proteins / metabolism
  • MicroRNAs* / genetics
  • Nucleotides / metabolism
  • RNA Stability
  • RNA, Messenger / genetics
  • RNA, Messenger / metabolism

Substances

  • MicroRNAs
  • Argonaute Proteins
  • Nucleotides
  • RNA, Messenger