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.

Additional Metadata
Persistent URL dx.doi.org/10.1038/s41467-017-02582-1, hdl.handle.net/1765/104279
Journal Nature Communications
Citation
Rehage, N. (Nina), Davydova, E. (Elena), Conrad, C. (Christine), Behrens, G. (Gesine), Maiser, A. (Andreas), Stehklein, J.E. (Jenny E.), … Heissmeyer, V. (Vigo). (2018). Binding of NUFIP2 to Roquin promotes recognition and regulation of ICOS mRNA. Nature Communications, 9(1). doi:10.1038/s41467-017-02582-1