Abstract

Although the RRM domain is defined as an RNA binding module (PFAM:PF00076), some RRMs have been found to bind to peptide linear motifs. A subgroup of RRMs termed UHMs have lost the ability to bind RNA, functioning instead as protein interacting domains (see ELM entry LIG_ULM_U2AF65_1). However some RNA-binding RRMs have also been shown to have linear motif binding capability (Rideau et al, 2006). The PRI peptide motif [S/G][L/I]LGxxP was characterized in the murine Raver1 protein, which is a splicing corepressor acting in combination with the well-characterized splicing repressor PTB. The motif was originally identified as being essential for splicing repressor activity when fragments of Raver1 were artificially recruited to a substrate pre-mRNA by fusion with MS2 coat protein RNA binding domain. Subsequently the same motif was found to be sufficient for interaction with PTB. NMR analysis characterized the interaction of the motif with PTB, indicating that it docked onto the dorsal surface of RRM2, with no other interactions detected within PTB. PRI may occur in other RNA processing proteins e.g. matrin3 matches the consensus motif and binds to PTB, while the uncharacterised RRM protein RBM16 has 5 PRI motif matches. Open questions are: how general is this peptide-binding property and are there many other motifs binding to RRMs?