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Convergence of multiple RNA-silencing pathways on GW182/TNRC6
Thomas Welte1, Alison Goulois2, Michael B Stadler3
1Friedrich Miescher Institute for Biomedical Research, Basel, Switzerland; Department of Medicine IV, Medical Center, Faculty of Medicine, University of Freiburg, Freiburg, Germany.
Molecular Cell
|June 27, 2023
Summary
The RNA-binding protein TRIM71 interacts with TNRC6/GW182 to silence target messenger RNAs (mRNAs). This interaction reveals a shared microRNA-like silencing activity across multiple pathways, regulated by TNRC6 as a central hub.
Area of Science:
- Molecular Biology
- Developmental Biology
- RNA Biology
Background:
- TRIM71/LIN-41 is a conserved RNA-binding protein crucial for development and disease.
- TRIM71 targets messenger RNAs (mRNAs) via hairpin motifs, but its silencing mechanisms are unclear.
- TNRC6/GW182 is a key protein in the microRNA-induced silencing complex (miRISC).
Purpose of the Study:
- To elucidate the molecular mechanisms by which TRIM71 silences target mRNAs.
- To investigate the interaction between TRIM71 and the microRNA-induced silencing complex (miRISC).
- To understand how TRIM71 contributes to gene regulation in developmental processes.
Main Methods:
- Investigated TRIM71-mediated mRNA silencing using biochemical assays.
- Analyzed the interaction between TRIM71, TNRC6/GW182, AGO2, and UPF1.
- Studied the impact of TNRC6 protein levels on silencing pathway competition.
Main Results:
- TRIM71 represses target mRNAs through an RNA-dependent interaction with TNRC6/GW182.
- AGO2, TRIM71, and UPF1 independently recruit TNRC6 to specific transcripts for silencing.
- Limited cellular TNRC6 levels create competition among these silencing pathways.
Conclusions:
- A microRNA-like silencing activity is shared across different mRNA silencing pathways.
- TNRC6 acts as a central hub, integrating the activities of multiple silencing pathways.
- TRIM71's interaction with TNRC6 highlights a conserved mechanism for developmental gene regulation.
Keywords:
AGO1GW182LIN41TNRC6TRIM71UPF1congenital hydrocephalusmiRNApost-transcriptional gene regulationstem cellMore Related Videos
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