English
 
Help Privacy Policy Disclaimer
  Advanced SearchBrowse

Item

ITEM ACTIONSEXPORT

Released

Journal Article

Human DDX6 regulates translation and decay of inefficiently translated mRNAs

MPS-Authors
/persons/resource/persons272040

Weber,  R       
Department Biochemistry, Max Planck Institute for Developmental Biology, Max Planck Society;

/persons/resource/persons273100

Wohlbold,  L
Department Biochemistry, Max Planck Institute for Developmental Biology, Max Planck Society;

/persons/resource/persons272371

Chang,  C-T       
Department Biochemistry, Max Planck Institute for Developmental Biology, Max Planck Society;

External Resource
No external resources are shared
Fulltext (restricted access)
There are currently no full texts shared for your IP range.
Fulltext (public)
There are no public fulltexts stored in PuRe
Supplementary Material (public)
There is no public supplementary material available
Citation

Weber, R., Wohlbold, L., & Chang, C.-T. (2024). Human DDX6 regulates translation and decay of inefficiently translated mRNAs. eLife, Epub ahead. doi:10.7554/eLife.92426.1.


Cite as: https://hdl.handle.net/21.11116/0000-000D-DC36-F
Abstract
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.