PT  - JOURNAL ARTICLE
AU  - Markus Terrey
AU  - Scott I. Adamson
AU  - Jeffrey H. Chuang
AU  - Susan L. Ackerman
TI  - Defects in translation-dependent quality control pathways lead to convergent molecular and neurodevelopmental pathology
AID  - 10.1101/2021.01.25.428167
DP  - 2021 Jan 01
TA  - bioRxiv
PG  - 2021.01.25.428167
4099  - http://biorxiv.org/content/early/2021/01/25/2021.01.25.428167.short
4100  - http://biorxiv.org/content/early/2021/01/25/2021.01.25.428167.full
AB  - 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 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 factor Upf2. These data reveal that these quality control pathways that function to mitigate errors at distinct steps in translation can evoke similar cellular responses.Competing Interest StatementThe authors have declared no competing interest.