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 may be regulated differently from canonical translation is poorly understood. Here, we used start codon-specific 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 multiple non-AUG-encoded reporters and the endogenous GUG-encoded DAP5 (eIF4G2/p97) mRNA is resistant to cycloheximide (CHX), a translation inhibitor that severely slows but does not completely abrogate elongation. Our data suggest that slowly elongating ribosomes can lead to queuing/stacking of sc

SUBMITTER: Kearse MG 

PROVIDER: S-EPMC6601509 | biostudies-literature | 2019 Jul

REPOSITORIES: biostudies-literature