A translational silencing function of MCPIP1/Regnase-1 specified by the target site context

Nucleic Acids Research
Gesine BehrensHelmut Holtmann

Abstract

The expression of proteins during inflammatory and immune reactions is coordinated by post-transcriptional mechanisms. A particularly strong suppression of protein expression is exerted by a conserved translational silencing element (TSE) identified in the 3' UTR of NFKBIZ mRNA, which is among the targets of the RNA-binding proteins Roquin-1/2 and MCPIP1/Regnase-1. We present evidence that in the context of the TSE MCPIP1, so far known for its endonuclease activity toward mRNAs specified by distinct stem-loop (SL) structures, also suppresses translation. Overexpression of MCPIP1 silenced translation in a TSE-dependent manner and reduced ribosome occupancy of the mRNA. Correspondingly, MCPIP1 depletion alleviated silencing and increased polysomal association of the mRNA. Translationally silenced NFKBIZ or reporter mRNAs were mostly capped, polyadenylated and ribosome associated. Furthermore, MCPIP1 silenced also cap-independent, CrPV-IRES-dependent translation. This suggests that MCPIP1 suppresses a post-initiation step. The TSE is predicted to form five SL structures. SL4 and 5 resemble target structures reported for MCPIP1 and together were sufficient for MCPIP1 binding and mRNA destabilization. Translational silencing, howeve...Continue Reading

References

Jun 15, 1992·Proceedings of the National Academy of Sciences of the United States of America·M Gossen, H Bujard
Sep 1, 1997·Nucleic Acids Research·S F AltschulD J Lipman
Aug 31, 2000·Journal of Molecular Biology·C NotredameJ Heringa
Aug 28, 2004·EMBO Reports·Tatyana V PestovaChristopher U T Hellen
Apr 17, 2007·PLoS Computational Biology·Sebastian WillRolf Backofen
Jan 8, 2008·The Journal of Biological Chemistry·Jian LiangMingui Fu
Mar 28, 2008·The Journal of Biological Chemistry·Jianli NiuPappachan E Kolattukudy
Jul 22, 2008·Virus Research·Peter J Lukavsky
Nov 19, 2008·BMC Bioinformatics·Stephan H BernhartPeter F Stadler
Nov 26, 2011·Algorithms for Molecular Biology : AMB·Ronny LorenzIvo L Hofacker
Jan 18, 2013·Archaea : an International Microbiological Journal·Jennifer GebetsbergerNorbert Polacek
Mar 19, 2013·Biochimica Et Biophysica Acta·Takuya Uehata, Shizuo Akira
Dec 18, 2013·Science·Ophir ShalemFeng Zhang
Apr 5, 2014·Journal of Interferon & Cytokine Research : the Official Journal of the International Society for Interferon and Cytokine Research·Christopher TiedjeMatthias Gaestel
Feb 13, 2016·Current Opinion in Immunology·Katharina M Jeltsch, Vigo Heissmeyer

❮ Previous
Next ❯

Citations

Mar 29, 2019·BioEssays : News and Reviews in Molecular, Cellular and Developmental Biology·Rosario Francisco-VelillaEncarnacion Martinez-Salas
Sep 11, 2019·Nature Neuroscience·Jordi Fernandez-AlbertAngel Barco
Aug 16, 2018·Frontiers in Immunology·Dirk Baumjohann, Vigo Heissmeyer
Feb 8, 2019·Respiratory Research·Sanjana Mahadev BhatChandrashekhar Charavaryamath
Apr 7, 2021·The Journal of Experimental Medicine·Numana BhatRobert C Rickert
Sep 7, 2021·Immunological Reviews·Benoit P NicoletMonika C Wolkers

❮ Previous
Next ❯

Methods Mentioned

BETA
transfection
pulldown
immunoprecipitation
electrophoresis
flow cytometry
deubiquitination
pulldowns

Software Mentioned

Tcoffee
RNAalifold
ViennaRNA package
BLAST
BLASTn
BLAT
mLocarna

Related Concepts

Related Feeds

CREs: Gene & Cell Therapy

Gene and cell therapy advances have shown promising outcomes for several diseases. The role of cis-regulatory elements (CREs) is crucial in the design of gene therapy vectors. Here is the latest research on CREs in gene and cell therapy.

Anti-inflammatory Treatments

A drug or substance that reduces inflammation (redness, swelling, and pain) in the body. Anti-inflammatory agents block certain substances in the body that cause inflammation and swelling. Discover the latest research on anti-inflammatory treatments here