Activation of 5'-3' exoribonuclease Xrn1 by cofactor Dcs1 is essential for mitochondrial function in yeast.

Proceedings of the National Academy of Sciences of the United States of America
Flore SinturelLionel Bénard

Abstract

The scavenger decapping enzyme Dcs1 has been shown to facilitate the activity of the cytoplasmic 5'-3' exoribonuclease Xrn1 in eukaryotes. Dcs1 has also been shown to be required for growth in glycerol medium. We therefore wondered whether the capacity to activate RNA degradation could account for its requirement for growth on this carbon source. Indeed, a catalytic mutant of Xrn1 is also unable to grow in glycerol medium, and removal of the nuclear localization signal of Rat1, the nuclear homolog of Xrn1, restores glycerol growth. A cytoplasmic 5'-3' exoribonuclease activity is therefore essential for yeast growth on glycerol, suggesting that Xrn1 activation by Dcs1 is physiologically important. In fact, Xrn1 is essentially inactive in the absence of Dcs1 in vivo. We analyzed the role of Dcs1 in the control of exoribonuclease activity in vitro and propose that Dcs1 is a specific cofactor of Xrn1. Dcs1 does not stimulate the activity of other 5'-3' exoribonucleases, such as Rat1, in vitro. We demonstrate that Dcs1 improves the apparent affinity of Xrn1 for RNA and that Xrn1 and Dcs1 can form a complex in vitro. We examined the biological significance of this regulation by performing 2D protein gel analysis. We observed that a s...Continue Reading

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Citations

Jul 30, 2014·Proceedings of the National Academy of Sciences of the United States of America·Siddharth Shukla, Roy Parker
Sep 8, 2015·Cell Reports·Flore SinturelLionel Benard
Aug 11, 2015·Nature Chemical Biology·Ancilla NeuRemco Sprangers
Apr 20, 2014·Biochimica Et Biophysica Acta·Adina L MilacAnna Wypijewska del Nogal
Mar 23, 2013·Biochimica Et Biophysica Acta·Vinay K NagarajanPamela J Green
Apr 2, 2013·Molecular Cell·Gabriel D BosséMartin J Simard
Aug 5, 2016·Journal of Medicinal Chemistry·Alyssa N CalderKevin J Hodgetts
Aug 16, 2018·Wiley Interdisciplinary Reviews. RNA·Benjamin P Towler, Sarah F Newbury
Aug 27, 2014·Molecular and Cellular Biology·Katherine A Braun, Elton T Young
Mar 13, 2014·Molecular Microbiology·Elisabeth J WurtmannNitin S Baliga
Oct 23, 2018·Wiley Interdisciplinary Reviews. RNA·Susanne Kramer, Alexander G McLennan
Aug 24, 2013·Cell Cycle·Oussama MezianeMartin J Simard
Mar 5, 2015·Journal of Cell Science·Luciana LuchelliGraciela L Boccaccio
Aug 17, 2021·The Journal of Infectious Diseases·Xiaojing ZhengToni Darville
Sep 2, 2021·Cerebral Cortex·Iva SalamonMegerditch Kiledjian
May 24, 2015·RNA·Mi ZhouMegerditch Kiledjian

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