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Related Experiment Video

Updated: Jun 4, 2025

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mRNA decay pre-complex assembly drives timely cell-state transitions during differentiation.

Hideyuki Komori¹, Geeta Rastogi¹, John Paul Bugay²

¹Life Sciences Institute, University of Michigan, Ann Arbor, MI 48109, USA.

|December 31, 2024

Summary

Ubiquitin-specific protease 5 (Usp5) interacts with the Drosophila RNA-binding protein Brat to regulate mRNA degradation. This interaction is crucial for timely cell-state transitions during development.

Keywords:

Brat CP: Developmental biology CP: Molecular biology Drosophila Usp5 cell state transitions deadenylase complexes differentiation mRNA decay maternal mRNAs neuroblast

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Published on: May 9, 2020

Area of Science:

Developmental biology
Molecular biology
Genetics

Background:

Cell-state transitions during differentiation rely on precise control of mRNA stability and translation.
The Drosophila RNA-binding protein brain tumor (Brat) is known to degrade target transcripts in specific developmental stages.

Purpose of the Study:

To identify novel interactors of Brat involved in mRNA degradation.
To elucidate the mechanism by which Brat-mediated mRNA degradation is regulated during neural development.

Main Methods:

Yeast three-hybrid screening to identify Brat interactors.
Immunoprecipitation and Western blotting to confirm protein interactions.
Analysis of mRNA levels and protein localization in Drosophila melanogaster.

Main Results:

Ubiquitin-specific protease 5 (Usp5) was identified as a Brat interactor essential for target mRNA degradation.
Usp5 facilitates the formation of the Brat-deadenylase pre-complex in neural stem cells.
The adaptor protein Miranda regulates Brat activity by binding to its RNA-binding domain, with its displacement activating the complex in immature neural progenitors.

Conclusions:

Usp5 plays a critical role in assembling the Brat-deadenylase complex, poised for activation.
Regulation of Brat-deadenylase complex assembly and activity by Miranda is key to timely developmental transitions.
This mechanism ensures precise control over gene expression during differentiation.