| Functional site
class: |
RRM domain ligands |
Functional site description: |
Although the primary role of RRM domains is to bind RNA, a second function for some RRMs is to bind to peptide motifs in other RNA processing factors. The PRI motif, originally characterized in Raver1, interacts with the “dorsal” surface of RRM2 of PTB. A ternary complex can form with RNA ligand bound to the beta sheet surface of RRM2 and the PRI motif to the alpha helical surface. |
| ELM(s): |
LIG_RRM_PRI_1 |
| LIG_RRM_PRI_1 description: |
The peptide motif [S/G][L/I]LGxxP was characterized in the Raver1 protein, which has been characterized as 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 (Rideau et al., 2006). Subsequently the same motif was found to be sufficient for interaction with GST-PTB in a pull-down assay. 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. The [S/G][L/I]LGxxP motif was derived by alanine scanning mutagenesis through amino acids 496-507 of mouse raver1, which contains the founder motif SLLGEPP. This was followed by more extensive mutation at positions 1-3 of the motif e.g. the two leucines were mutated to I, V and A. Following this, additional motifs in raver1 and hnRNPL were tested. The motif also matches the sequence conservation of these proteins’ homologues. |
| Pattern: |
.[ilvm]lg..p. |
| Present in taxon(s): |
Chordata |
| Not represented in taxon(s): |
|
 See instances for LIG_RRM_PRI_1
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?
Selected references
This ELM has been assigned the following Gene Ontology (GO) terms for biological process, cellular component and molecular function.
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Biological Process |
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negative regulation of nuclear mRNA splicing, via spliceosome
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mRNA splice site selection
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Cellular Component |
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nucleus |
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heterogeneous nuclear ribonucleoprotein complex |
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Molecular Function |
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protein domain specific binding |
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