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MicroRNA Amplification and Recognition through Locked-nucleic-acid In situ Hybridization as A Novel Detection and Quantification Method
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MicroRNA Amplification and Recognition through Locked-nucleic-acid In situ Hybridization as A Novel Detection and Quantification Method

Published on: October 7, 2025

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A novel class of microRNA-recognition elements that function only within open reading frames

Kai Zhang1, Xiaorong Zhang2, Zhiqiang Cai1

  • 1State Key Laboratory of Virology, Hubei Key Laboratory of Cell Homeostasis, College of Life Sciences, Wuhan University, Wuhan, China.

Nature Structural & Molecular Biology
|October 10, 2018
PubMed

Insights

This study identifies novel microRNA (miRNA) recognition elements exclusively in protein-coding sequences. These CDS-targeted miRNAs regulate gene expression via ribosome stalling, distinct from 3' UTR targeting mechanisms.

Area of Science:

  • Molecular Biology
  • Genetics
  • Post-transcriptional Regulation

Background:

  • MicroRNAs (miRNAs) typically target 3' untranslated regions (3' UTRs) of mRNAs for post-transcriptional gene silencing.
  • While miRNAs can target protein-coding sequences (CDS), their mechanisms were thought to be uniform regardless of target site location.

Purpose of the Study:

  • To characterize a novel class of miRNA-recognition elements (MREs) found exclusively within CDS regions.
  • To elucidate the distinct mechanisms and functional consequences of miRNA targeting within CDS compared to 3' UTRs.

Main Methods:

  • Functional assays to characterize CDS-targeted MREs.
  • Mechanistic studies involving Argonaute and GW182 proteins.
  • Analysis of translation repression and mRNA stability.

Main Results:

  • A class of MREs functioning exclusively in CDS was identified.
  • CDS-targeted miRNAs require extensive 3'-side base-pairing and operate in an Argonaute-dependent, GW182-independent manner.
  • These miRNAs repress translation by inducing transient ribosome stalling, not mRNA destabilization.

Conclusions:

  • CDS-targeted miRNAs employ distinct mechanisms compared to 3' UTR-targeted miRNAs.
  • This suggests a potential role for CDS-targeted miRNAs in translational quality control in mammalian cells.

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