Dynamic post-transcriptional regulation by Mrn1 links cell wall homeostasis to mitochondrial structure and function.

Kendra Reynaud,Molly Brothers,Michael Ly,Nicholas T Ingolia,Anita K Hopper

doi:10.1371/journal.pgen.1009521

Kendra Reynaud, Molly Brothers + Show 3 more

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https://doi.org/10.1371/journal.pgen.1009521

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Journal: PLoS Genetics	Publication Date: Apr 15, 2021
Citations: 7	License type: CC BY 4.0

Affiliation: QB3, University of California, Berkeley

Abstract

The RNA-binding protein Mrn1 in Saccharomyces cerevisiae targets over 300 messenger RNAs, including many involved in cell wall biogenesis. The impact of Mrn1 on these target transcripts is not known, however, nor is the cellular role for this regulation. We have shown that Mrn1 represses target mRNAs through the action of its disordered, asparagine-rich amino-terminus. Its endogenous targets include the paralogous SUN domain proteins Nca3 and Uth1, which affect mitochondrial and cell wall structure and function. While loss of MRN1 has no effect on fermentative growth, we found that mrn1Δ yeast adapt more quickly to respiratory conditions. These cells also have enlarged mitochondria in fermentative conditions, mediated in part by dysregulation of NCA3, and this may explain their faster switch to respiration. Our analyses indicated that Mrn1 acts as a hub for integrating cell wall integrity and mitochondrial biosynthesis in a carbon-source responsive manner.

Highlights

Gene expression is regulated post-transcriptionally by numerous proteins that recognize specific transcripts and modulate their translation, localization, and decay [1]
We establish that the yeast RNA-binding protein Mrn1 controls a gene expression program that links the mitochondrion with the yeast cell wall
Mrn1 binds hundreds of target messenger RNAs (mRNAs), which are enriched for functions in cell wall organization and biogenesis

Summary

Introduction

Gene expression is regulated post-transcriptionally by numerous proteins that recognize specific transcripts and modulate their translation, localization, and decay [1]. An individual RNA-binding protein (RBP) can target dozens or hundreds of different messenger RNAs (mRNAs), thereby controlling a post-transcriptional regulon of functionally related genes [2]. These coordinated regulatory programs allow cells to quickly remodel gene expression in response to changing growth conditions [3] and acute stress [4]. Mrn has been reported to bind over 300 mRNAs, and these targets are enriched for transcripts that encode cell wall biogenesis and regulatory proteins [5] Many of these target transcripts are shared among a subset of other yeast RBPs including Khd, Pub, Scp160, and Ssd1 [5]. No overt cell wall phenotypes have been linked to the loss of mrn, and prior work has instead identified genetic interactions with chromatin remodelers and splicing factors [6]

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