|
| Status |
Public on Oct 06, 2020 |
| Title |
4EHP and GIGYF1/2 induce translation-coupled messenger RNA decay [Wildtype and ZNF598-null] |
| Organism |
Homo sapiens |
| Experiment type |
Expression profiling by high throughput sequencing
|
| Summary |
Although canonical mRNA degradation is generally recognized to be translation dependent, our understanding of the molecular events that coordinate ribosome movement with the decay machinery is still limited. Here, we show that the 4EHP–GIGYF1/2 complex triggers co-translational mRNA decay as a result of altered ribosome activity during elongation. Human cells lacking 4EHP and GIGYF1 and 2 proteins accumulate transcripts known to be degraded in a translation dependent manner or with prominent ribosome pausing. These include mRNAs encoding secretory and membrane-bound proteins or specific tubulin isotypes, among others. 4EHP–GIGYF1/2 fails to reduce target mRNA levels in the absence of ribosome stalling or upon disruption of its interaction with the cap structure, DDX6 and a GYF domain-associated protein. Our studies reveal how a repressor complex linked to neurological disorders minimizes the protein output of a subset of mRNAs.
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| |
|
| Overall design |
Two cell types with two biological replicates analysed using RNA-Seq and Ribo-Seq
|
| |
|
| Contributor(s) |
Weber R, Igreja C |
| Citation(s) |
33053355 |
| |
| Submission date |
Apr 24, 2020 |
| Last update date |
Jan 15, 2021 |
| Contact name |
Ramona Weber |
| E-mail(s) |
ramona.weber@uzh.ch
|
| Organization name |
University of Zurich
|
| Department |
Institute for Regenerative Medicine
|
| Street address |
Wagistrasse 12
|
| City |
Schlieren |
| ZIP/Postal code |
8952 |
| Country |
Switzerland |
| |
|
| Platforms (1) |
| GPL21290 |
Illumina HiSeq 3000 (Homo sapiens) |
|
| Samples (8)
|
| GSM4495441 |
Wild-type, control replicate 1 for RNA-seq |
| GSM4495442 |
Wild-type, control replicate 2 for RNA-seq |
| GSM4495443 |
ZNF598-null replicate 1 for RNA-seq |
| GSM4495444 |
ZNF598-null replicate 2 for RNA-seq |
| GSM4495445 |
Wild-type, control replicate 1 for Ribo-seq |
| GSM4495446 |
Wild-type, control replicate 2 for Ribo-seq |
| GSM4495447 |
ZNF598-null replicate 1 for Ribo-seq |
| GSM4495448 |
ZNF598-null replicate 2 for Ribo-seq |
|
| Relations |
| BioProject |
PRJNA627881 |
| SRA |
SRP258289 |
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