A network of RNA-binding proteins controls translation efficiency to activate anaerobic metabolism.

Abstract:

:Protein expression evolves under greater evolutionary constraint than mRNA levels, and translation efficiency represents a primary determinant of protein levels during stimuli adaptation. This raises the question as to the translatome remodelers that titrate protein output from mRNA populations. Here, we uncover a network of RNA-binding proteins (RBPs) that enhances the translation efficiency of glycolytic proteins in cells responding to oxygen deprivation. A system-wide proteomic survey of translational engagement identifies a family of oxygen-regulated RBPs that functions as a switch of glycolytic intensity. Tandem mass tag-pulse SILAC (TMT-pSILAC) and RNA sequencing reveals that each RBP controls a unique but overlapping portfolio of hypoxic responsive proteins. These RBPs collaborate with the hypoxic protein synthesis apparatus, operating as a translation efficiency checkpoint that integrates upstream mRNA signals to activate anaerobic metabolism. This system allows anoxia-resistant animals and mammalian cells to initiate anaerobic glycolysis and survive hypoxia. We suggest that an oxygen-sensitive RBP cluster controls anaerobic metabolism to confer hypoxia tolerance.

journal_name

Nat Commun

journal_title

Nature communications

authors

Ho JJD,Balukoff NC,Theodoridis PR,Wang M,Krieger JR,Schatz JH,Lee S

doi

10.1038/s41467-020-16504-1

subject

Has Abstract

pub_date

2020-05-29 00:00:00

pages

2677

issue

1

issn

2041-1723

pii

10.1038/s41467-020-16504-1

journal_volume

11

pub_type

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