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Defects in translation-dependent quality control pathways lead to convergent molecular and neurodevelopmental pathology

Authors :
Scott I Adamson
Susan L. Ackerman
Jeffrey H. Chuang
Markus Terrey
Publication Year :
2021
Publisher :
Cold Spring Harbor Laboratory, 2021.

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 thein vivodefects that arise in the absence of these pathways are poorly understood. Here, we show that the NGD/NSD factorsPeloandHbs1lare critical for cerebellar neurogenesis but expendable for survival of these neurons after development. Analysis of mutant embryonic fibroblasts revealed translational pauses, alteration of signaling pathways, and translational reprogramming. Similar effects on signaling pathways, the translatome and cerebellar development were observed upon deletion of the NMD factorUpf2.These data reveal that these quality control pathways that function to mitigate errors at distinct steps in translation can evoke similar cellular responses.

Details

Database :
OpenAIRE
Accession number :
edsair.doi...........c44c6d342a59d5c3def23a1ced8821ec