| 1 |
DDX3X and specific initiation factors modulate FMR1 repeat‐associated non‐AUG‐initiated translation
|
|
|
|
BASE
|
|
Show details
|
|
|
| 2 |
High-throughput screening yields several small-molecule inhibitors of repeat-associated non-AUG translation
|
|
|
|
In: J Biol Chem (2019)
|
|
BASE
|
|
Show details
|
|
|
| 3 |
Ribosome queuing enables non-AUG translation to be resistant to multiple protein synthesis inhibitors
|
|
Kearse, Michael G.; Goldman, Daniel H.; Choi, Jiou; Nwaezeapu, Chike; Liang, Dongming; Green, Katelyn M.; Goldstrohm, Aaron C.; Todd, Peter K.; Green, Rachel; Wilusz, Jeremy E.. - : Cold Spring Harbor Laboratory Press, 2019
|
|
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 scanning preinitiation complexes (PICs), preferentially enhancing recognition of weak non-AUG start codons. Consistent with this model, limiting PIC formation or scanning sensitizes non-AUG translation to CHX. We further found that non-AUG translation is resistant to other inhibitors that target ribosomes within the coding sequence but not those targeting newly initiated ribosomes. Together, these data indicate that ribosome queuing enables mRNAs with poor initiation context—namely, those with non-AUG start codons—to be resistant to pharmacological translation inhibitors at concentrations that robustly inhibit global translation.
|
|
Keyword:
Research Paper
|
|
URL: https://doi.org/10.1101/gad.324715.119
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6601509/
http://www.ncbi.nlm.nih.gov/pubmed/31171704
|
|
BASE
|
|
Hide details
|
|
|
| 4 |
DDX3X and specific initiation factors modulate FMR1 repeat‐associated non‐AUG‐initiated translation
|
|
|
|
In: EMBO Rep (2019)
|
|
BASE
|
|
Show details
|
|
|
| 5 |
RAN translation at C9orf72-associated repeat expansions is selectively enhanced by the integrated stress response
|
|
|
|
BASE
|
|
Show details
|
|
|
| 6 |
CGG Repeat associated non-AUG translation utilizes a cap-dependent, scanning mechanism of initiation to produce toxic proteins
|
|
|
|
BASE
|
|
Show details
|
|
|
|
|
