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,
Journal Nature Communications
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