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RNF219 attenuates global mRNA decay through inhibition of CCR4-NOT complex-mediated deadenylation
Fabian Poetz1,2, Joshua Corbo3, Yevgen Levdansky3
1Division of Biochemistry, Mannheim Institute for Innate Immunoscience (MI3), Medical Faculty Mannheim, Heidelberg University, 68167, Mannheim, Germany.
Nature Communications
|December 10, 2021
Summary
RNF219 is identified as an E3 ligase that inhibits mRNA deadenylation by the CCR4-NOT complex. Its loss upon HDAC inhibition accelerates mRNA turnover, impacting gene expression regulation.
Area of Science:
- Molecular Biology
- Gene Regulation
- Biochemistry
Background:
- The CCR4-NOT complex is a key regulator of mRNA turnover.
- HDAC inhibition leads to accelerated mRNA degradation.
Purpose of the Study:
- To investigate acetylation-induced changes in the CCR4-NOT complex composition.
- To identify novel cofactors and their roles in mRNA regulation.
Main Methods:
- Purification of endogenously tagged NOT1 subunit of CCR4-NOT complex.
- Identification and characterization of RNF219 as an acetylation-regulated cofactor.
- Reconstitution of human CCR4-NOT complex and in vitro binding assays.
- Transcriptome-wide mRNA half-life measurements.
Main Results:
- RNF219 identified as an active RING-type E3 ligase associated with CCR4-NOT via NOT9.
- RNF219 inhibits deadenylation through interaction with the NOT9 module via a SLiM.
- RNF219 attenuates global mRNA turnover, with its RING domain playing a differential role.
- Loss of RNF219 upon HDAC inhibition contributes to accelerated mRNA turnover.
Conclusions:
- RNF219 acts as an inhibitor of CCR4-NOT-mediated deadenylation.
- RNF219's regulation by acetylation and its role in mRNA turnover are established.
- Findings provide insights into the mechanisms controlling mRNA stability and gene expression.
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