Conserved mechanism of Xrn1 regulation by glycolytic flux and protein aggregation

Kód výsledku v IS VaVaI

<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F68378041%3A_____%2F25%3A00603114" target="_blank" >RIV/68378041:_____/25:00603114 - isvavai.cz</a>

Výsledek na webu

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DOI - Digital Object Identifier

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Jazyk výsledku

angličtina

Název v původním jazyce

Conserved mechanism of Xrn1 regulation by glycolytic flux and protein aggregation

Popis výsledku v původním jazyce

Gene expression in eukaryotes is largely controlled by exoribonucleases that degrade decapped mRNAs in the 5’–3’ direction. Xrn1, the major yeast exoribonuclease, is regulated through changes in cellular localization linked to metabolic state. Under fermentable carbon conditions, Xrn1 is active in the cytosol, while carbon depletion leads to its sequestration at eisosomes and inactivation. We show that Xrn1 membrane binding depends on glycolytic flux rather than carbon source availability, is independent of TORC1, and requires Pil1 and Lsp1. The SH3-like domain of Xrn1 likely mediates this interaction. Notably, the human Xrn1 orthologue expressed in yeast shows similar behavior, localizing to eisosomes when glycolysis is halted. These findings reveal a conserved regulatory mechanism from yeast to humans.

Název v anglickém jazyce

Conserved mechanism of Xrn1 regulation by glycolytic flux and protein aggregation

Popis výsledku anglicky

Gene expression in eukaryotes is largely controlled by exoribonucleases that degrade decapped mRNAs in the 5’–3’ direction. Xrn1, the major yeast exoribonuclease, is regulated through changes in cellular localization linked to metabolic state. Under fermentable carbon conditions, Xrn1 is active in the cytosol, while carbon depletion leads to its sequestration at eisosomes and inactivation. We show that Xrn1 membrane binding depends on glycolytic flux rather than carbon source availability, is independent of TORC1, and requires Pil1 and Lsp1. The SH3-like domain of Xrn1 likely mediates this interaction. Notably, the human Xrn1 orthologue expressed in yeast shows similar behavior, localizing to eisosomes when glycolysis is halted. These findings reveal a conserved regulatory mechanism from yeast to humans.

Druh

X - Nezařazeno

CEP obor

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OECD FORD obor

10601 - Cell biology

Projekt

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Návaznosti

I - Institucionalni podpora na dlouhodoby koncepcni rozvoj vyzkumne organizace

Rok uplatnění

2025

Kód důvěrnosti údajů

S - Úplné a pravdivé údaje o projektu nepodléhají ochraně podle zvláštních právních předpisů