Document Type

Article

Publication Date

4-26-2021

Publication Title

Elife

Keywords

JGM

JAX Source

Elife 2021 Apr 26; 10:e66904

Volume

10

ISSN

2050-084X

PMID

33899734

DOI

https://doi.org/10.7554/elife.66904

Grant

NS094637

Abstract

Translation-dependent quality control pathways such as no-go decay (NGD), non-stop decay (NSD), and nonsense-mediated decay (NMD) govern protein synthesis and proteostasis by resolving non-translating ribosomes and preventing the production of potentially toxic peptides derived from faulty and aberrant mRNAs. However, how translation is altered and the in vivo defects that arise in the absence of these pathways are poorly understood.

Here, we show that the NGD/NSD factors Pelo and Hbs1l are critical in mice for cerebellar neurogenesis but expendable for survival of these neurons after development. Analysis of mutant mouse embryonic fibroblasts revealed translational pauses, alteration of signaling pathways, and translational reprogramming. Similar effects on signaling pathways, including mTOR activation, the translatome and mouse cerebellar development were observed upon deletion of the NMD factor Upf2. Our data reveal that these quality control pathways that function to mitigate errors at distinct steps in translation can evoke similar cellular responses.

Comments

This article is distributed under the terms of the Creative Commons Attribution License.

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