RBM10: Harmful or helpful-many factors to consider

Abstract

RBM10 is an RNA binding motif (RBM) protein expressed in most, if not all, human and animal cells. Interest in RBM10 is rapidly increasing and its clinical importance is highlighted by its identification as the causative agent of TARP syndrome, a developmental condition that significantly impacts affected children. RBM10's cellular functions are beginning to be explored, with initial studies demonstrating a tumor suppressor role. Very recently, however, contradictory results have emerged, suggesting a tumor promoter role for RBM10. In this review, we describe the current state of knowledge on RBM10, and address this dichotomy in RBM10 function. Furthermore, we discuss what may be regulating RBM10 function, particularly the importance of RBM10 alternative splicing, and the relationship between RBM10 and its paralogue, RBM5. As RBM10-related work is gaining momentum, it is critical that the various aspects of RBM10 molecular biology revealed by recent studies be considered moving forward. It is only if these recent advances in RBM10 structure and function are considered that a clearer insight into RBM10 function, and the disease states with which RBM10 mutation is associated, will be gained.

Keywords: RBM10; RBM5; RNA binding proteins; SMN; TARP; regulation.

Figure 1

Selected RBM10 and RBM5 consensus functional motifs. Translated RBM10 (A) and RBM5 (B) exons are represented by boxes. Numbers indicated within a box designate the exon it represents within the corresponding transcript. Box size does not represent exon length. Location of RBM10 and RBM5 consensus functional motifs are indicated by the thick line above the corresponding box(es), and the type of motif is indicated. NLS refers to nuclear localization signal. Principal RBM10 alternative splice variants are also included (A), with the orange line representing the absence of a GTG RNA triplet at that location (end of exon 10)

Figure 2

RBM10 interacting factors. Factors demonstrated to interact with RBM10 RNA (blue) and RBM10 protein (RNA factors in green, and protein factors in purple) are indicated. Established functional consequences of the interactions are indicated (if known). Text on arrows indicates which RBM10 isoform was involved in the study (as indicated by the referenced manuscript's published NCBI accession number or GenBank ID, when available). IP RBM10 indicates that RBM10‐interacting factors were identified by immunoprecipitation of RBM10 with an antibody with an immunogen sequence more homologous to RBM10v1 than RBM10v2 (the last 14 amino‐acids of its 81 amino acid immunogen sequence were not specific for RBM10v2) (Sigma HPA034972)