Binding of NUFIP2 to Roquin promotes recognition and regulation of ICOS mRNA.
basic_science · Level V
Where this comes from
- Record sourced from PubMed, PMID 29352114.
- Also identified by DOI 10.1038/s41467-017-02582-1 and PMC identifier 5775257.
- Licence recorded as CC BY.
- The licence permits redistribution, so the abstract is shown in full and the full text is available from the publisher.
Abstract
The ubiquitously expressed RNA-binding proteins Roquin-1 and Roquin-2 are essential for appropriate immune cell function and postnatal survival of mice. Roquin proteins repress target mRNAs by recognizing secondary structures in their 3'-UTRs and by inducing mRNA decay. However, it is unknown if other cellular proteins contribute to target control. To identify cofactors of Roquin, we used RNA interference to screen ~1500 genes involved in RNA-binding or mRNA degradation, and identified NUFIP2 as a cofactor of Roquin-induced mRNA decay. NUFIP2 binds directly and with high affinity to Roquin, which stabilizes NUFIP2 in cells. Post-transcriptional repression of human ICOS by endogenous Roquin proteins requires two neighboring non-canonical stem-loops in the ICOS 3'-UTR. This unconventional cis-element as well as another tandem loop known to confer Roquin-mediated regulation of the Ox40 3'-UTR, are bound cooperatively by Roquin and NUFIP2. NUFIP2 therefore emerges as a cofactor that contributes to mRNA target recognition by Roquin.
Medical subject headings
- CD4-Positive T-Lymphocytes
- Inducible T-Cell Co-Stimulator Protein
- Nuclear Proteins
- RNA-Binding Proteins
- Receptors, OX40
- Repressor Proteins
- Ubiquitin-Protein Ligases