 |
 |
GEO help: Mouse over screen elements for information. |
|
| Status |
Public on Jun 05, 2019 |
| Title |
Ribosome queuing enables non-AUG translation to be resistant to multiple protein synthesis inhibitors |
| Organism |
Homo sapiens |
| Experiment type |
Other
Expression profiling by high throughput sequencing
|
| Summary |
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.
|
| |
|
| Overall design |
Measuring translational efficiency genome-wide in response to prolonged cyclohexamide treatment
|
| |
|
| Contributor(s) |
Kearse M, Goldman D, Choi J, Nwaezeapu C, Liang D, Green K, Goldstrohm A, Todd P, Green R, Wilusz J |
| Citation(s) |
31171704 |
| Submission date |
Jan 15, 2019 |
| Last update date |
Oct 06, 2023 |
| Contact name |
Daniel Goldman |
| E-mail(s) |
goldman@jhmi.edu
|
| Organization name |
Johns Hopkins School of Medicine
|
| Department |
Molecular Biology and Genetics
|
| Lab |
Rachel Green
|
| Street address |
725 N. Wolfe St.
|
| City |
Baltimore |
| State/province |
Maryland |
| ZIP/Postal code |
21205 |
| Country |
USA |
| |
|
| Platforms (1) |
| GPL16791 |
Illumina HiSeq 2500 (Homo sapiens) |
|
| Samples (12)
|
| GSM3562582 |
Vehicle-treated, replicate A footprints |
| GSM3562583 |
Vehicle-treated, replicate B footprints |
| GSM3562584 |
15 min-treated, replicate A footprints |
|
| Relations |
| BioProject |
PRJNA515197 |
| SRA |
SRP179458 |
| Supplementary file |
Size |
Download |
File type/resource |
| GSE125086_RNAseq_cds_rpkms.tsv.gz |
612.8 Kb |
(ftp)(http) |
TSV |
| GSE125086_TE_summary.csv.gz |
62.6 Kb |
(ftp)(http) |
CSV |
| GSE125086_cds_rpkms.tsv.gz |
516.9 Kb |
(ftp)(http) |
TSV |
SRA Run Selector |
| Raw data are available in SRA |
| Processed data are available on Series record |
|
|
|
|
 |
Less...
More...