Details zur Publikation

Kategorie Textpublikation
Referenztyp Zeitschriften
DOI 10.1093/nar/gky106
Lizenz creative commons licence
Titel (primär) A translational silencing function of MCPIP1/Regnase-1 specified by the target site context
Autor Behrens, G.; Winzen, R.; Rehage, N.; Dörrie, A.; Barsch, M.; Hoffmann, A.; Hackermüller, J. ORCID logo ; Tiedje, C.; Heissmeyer, V.; Holtmann, H.
Quelle Nucleic Acids Research
Erscheinungsjahr 2018
Department MOLSYB
Band/Volume 46
Heft 8
Seite von 4256
Seite bis 4270
Sprache englisch
UFZ Querschnittsthemen RU3;
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, however, required SL1–3 in addition. Thus the NFKBIZ TSE functions as an RNA element in which sequences adjacent to the site of interaction with MCPIP1 and dispensable for accelerated mRNA degradation extend the functional repertoire of MCPIP1 to translational silencing.
dauerhafte UFZ-Verlinkung
Behrens, G., Winzen, R., Rehage, N., Dörrie, A., Barsch, M., Hoffmann, A., Hackermüller, J., Tiedje, C., Heissmeyer, V., Holtmann, H. (2018):
A translational silencing function of MCPIP1/Regnase-1 specified by the target site context
Nucleic Acids Res. 46 (8), 4256 - 4270 10.1093/nar/gky106