|
| Status |
Public on Jan 23, 2024 |
| Title |
Human DDX6 regulates translation and decay of inefficiently translated mRNAs |
| Organism |
Homo sapiens |
| Experiment type |
Expression profiling by high throughput sequencing
|
| Summary |
Recent findings indicate that the translation elongation rate influences mRNA stability. One of the factors that has been implicated in this link between mRNA decay and translation speed is the yeast DEAD-box helicase Dhh1p. Here, we demonstrate that the human ortholog of Dhh1p, DDX6, triggers deadenylation-dependent decay of inefficiently translated mRNAs in human cells. DDX6 interacts with the ribosome through the Phe-Asp-Phe (FDF) motif in its RecA2 domain. Furthermore, RecA2-mediated interactions and ATPase activity are both required for DDX6 to destabilize inefficiently translated mRNAs. Using ribosome profiling and RNA sequencing, we identified two classes of endogenous mRNAs that are regulated in a DDX6-dependent manner. The identified targets are either translationally regulated or regulated at the steady-state-level and either exhibit signatures of poor overall translation or of locally reduced ribosome translocation rates. Transferring the identified sequence stretches into a reporter mRNA caused translation- and DDX6-dependent degradation of the reporter mRNA. In summary, these results identify DDX6 as a crucial regulator of mRNA translation and decay triggered by slow ribosome movement and provide insights into the mechanism by which DDX6 destabilizes inefficiently translated mRNAs.
|
| |
|
| Overall design |
Two cell types with two biological replicates analysed using RNA-Seq and Ribo-Seq
|
| Web link |
https://doi.org/10.7554/eLife.92426.1
|
| |
|
| Contributor(s) |
Weber R, Chang C |
| Citation(s) |
38989862 |
| |
| Submission date |
May 08, 2023 |
| Last update date |
Aug 08, 2024 |
| 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)
|
| GSM7306528 |
Wild-type (DDX6-nul control) replicate 1 for RNA-seq |
| GSM7306529 |
Wild-type (DDX6-nul control) replicate 2 for RNA-seq |
| GSM7306530 |
DDX6-null replicate 1 for RNA-seq |
| GSM7306531 |
DDX6-null replicate 2 for RNA-seq |
| GSM7306532 |
Wild-type (DDX6-nul control) replicate 1 for Ribo-seq |
| GSM7306533 |
Wild-type (DDX6-nul control) replicate 2 for Ribo-seq |
| GSM7306534 |
DDX6-null replicate 1 for Ribo-seq |
| GSM7306535 |
DDX6-null replicate 2 for Ribo-seq |
|
| Relations |
| BioProject |
PRJNA970317 |
Less...
More...