Splicing Site Recognition by Synergy of Three Domains in Splicing Factor RBM10

Overview

Journal Biochemistry

Specialty Biochemistry

Date 2018 Feb 17

PMID 29450990

Citations 5

Authors

Pedro Serrano

John A Hammond

Michael Geralt

Kurt Wuthrich

Affiliations

Soon will be listed here.

Abstract

Splicing factor RBM10 and its close homologues RBM5 and RBM6 govern the splicing of oncogenes such as Fas, NUMB, and Bcl-X. The molecular architecture of these proteins includes zinc fingers (ZnFs) and RNA recognition motifs (RRMs). Three of these domains in RBM10 that constitute the RNA binding part of this splicing factor were found to individually bind RNAs with micromolar affinities. It was thus of interest to further investigate the structural basis of the well-documented high-affinity RNA recognition by RMB10. Here, we investigated RNA binding by combinations of two or three of these domains and discovered that a polypeptide containing RRM1, ZnF1, and RRM2 connected by their natural linkers recognizes a specific sequence of the Fas exon 6 mRNA with an affinity of 20 nM. Nuclear magnetic resonance structures of the RBM10 domains RRM1 and ZnF1 and the natural V354del isoform of RRM2 further confirmed that the interactions with RNA are driven by canonical RNA recognition elements. The well-known high-fidelity RNA splice site recognition by RBM10, and probably by RBM5 and RBM6, can thus be largely rationalized by a cooperative binding action of RRM and ZnF domains.

Citing Articles

Structural basis for specific RNA recognition by the alternative splicing factor RBM5.

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The RNA-Binding Motif Protein Family in Cancer: Friend or Foe?.

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