Other

Dataset Information

0

Ribosome queuing enables non-AUG translation to be resistant to multiple protein synthesis inhibitors


ABSTRACT: Aberrant translation initiation at non-AUG start codons is associated with multiple cancers and neurodegenerative diseases. Nevertheless, how non-AUG translation is regulated differently from canonical translation is poorly understood. We thus used start codon-selective  reporters and ribosome profiling to characterize how translation from non-AUG start codons responds to protein synthesis inhibitors in human cells. These analyses surprisingly revealed that translation of non-AUG reporters and the endogenous GUG-encoded DAP5 (eIF4G2/p97) mRNA are resistant to cycloheximide (CHX), a translation inhibitor which slows but does not completely abrogate elongation. Our data suggest that slowly elongating ribosomes cause queuing of scanning pre-initiation complexes (PIC), preferentially enhancing otherwise poor recognition of non-AUG start codons. Consistent with this model, limiting PIC formation or scanning sensitizes non-AUG translation to CHX. Moreover, PIC queuing can cause translation from an AUG codon in a poor context to become less sensitive to CHX. We further find that non-AUG translation is resistant to other inhibitors that target ribosomes within the coding sequence, but not those targeting newly initiated ribosomes. In total, these data indicate that ribosome queuing enables mRNAs with poor initiation context, namely those from non-AUG start codons, to be resistant to pharmacological inhibitors.

ORGANISM(S): Homo sapiens

PROVIDER: GSE125086 | GEO | 2019/06/05

REPOSITORIES: GEO

Dataset's files

Source:
Action DRS
Other
Items per page:
1 - 1 of 1

Similar Datasets

2021-11-24 | GSE176058 | GEO
2019-10-18 | GSE138599 | GEO
2017-12-21 | GSE108334 | GEO
2020-07-24 | GSE150375 | GEO
2022-02-21 | GSE184515 | GEO
2012-08-08 | E-GEOD-39561 | biostudies-arrayexpress
2023-10-03 | GSE244093 | GEO
2011-11-03 | E-GEOD-30839 | biostudies-arrayexpress
2016-02-15 | E-GEOD-72030 | biostudies-arrayexpress
2022-06-08 | GSE162043 | GEO