English
 
Help Privacy Policy Disclaimer
  Advanced SearchBrowse

Item

ITEM ACTIONSEXPORT

Released

Journal Article

A low-complexity region in human XRN1 directly recruits deadenylation and decapping factors in 5 '-3 ' messenger RNA decay.

MPS-Authors
/persons/resource/persons242922

Chen,  Y.
Department of Molecular Biology, MPI for Biophysical Chemistry, 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)

3176998.pdf
(Publisher version), 3MB

Supplementary Material (public)

3176998_Suppl.htm
(Supplementary material), 457KB

Citation

Chang, C. T., Muthukumar, S., Weber, R., Levdansky, Y., Chen, Y., Bhandari, D., et al. (2019). A low-complexity region in human XRN1 directly recruits deadenylation and decapping factors in 5 '-3 ' messenger RNA decay. Nucleic Acids Research, 47(17), 9282-9295. doi:10.1093/nar/gkz633.


Cite as: https://hdl.handle.net/21.11116/0000-0005-20DE-D
Abstract
XRN1 is the major cytoplasmic exoribonuclease in eukaryotes, which degrades deadenylated and decapped mRNAs in the last step of the 5'-3' mRNA decay pathway. Metazoan XRN1 interacts with decapping factors coupling the final stages of decay. Here, we reveal a direct interaction between XRN1 and the CCR4-NOT deadenylase complex mediated by a low-complexity region in XRN1, which we term the 'C-terminal interacting region' or CIR. The CIR represses reporter mRNA deadenylation in human cells when overexpressed and inhibits CCR4-NOT and isolated CAF1 deadenylase activity in vitro. Through complementation studies in an XRN1-null cell line, we dissect the specific contributions of XRN1 domains and regions toward decay of an mRNA reporter. We observe that XRN1 binding to the decapping activator EDC4 counteracts the dominant negative effect of CIR overexpression on decay. Another decapping activator PatL1 directly interacts with CIR and alleviates the CIR-mediated inhibition of CCR4-NOT activity in vitro. Ribosome profiling revealed that XRN1 loss impacts not only on mRNA levels but also on the translational efficiency of many cellular transcripts likely as a consequence of incomplete decay. Our findings reveal an additional layer of direct interactions in a tightly integrated network of factors mediating deadenylation, decapping and 5'-3' exonucleolytic decay.