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.

RBM10–TFE3 renal cell carcinoma characterised by paracentric inversion with consistent closely split signals in break‐apart fluorescence in‐situ hybridisation: study of 10 cases and a literature review

“…With regard to malignancies, RBM10 mutations have been detected in adenocarcinomas of the lung and pancreas . Both protumour and antitumour effects in terms of apoptosis, cell proliferation and expression of important tumour‐associated molecules have been described in different experimental settings . In patients with pancreatic ductal carcinoma, RBM10 mutations were reported to be associated with longer survival .…”

RBM10 regulates centriole duplication in HepG2 cells by ectopically assembling PLK4‐STIL complexes in the nucleus

“…Most studies on RBM10 have focused on its role of alternative splicing activity for its target genes to explain its biological functions in cancer, development and immunity (Atsumi et al, 2017;Loiselle & Sutherland, 2018). It is intriguing that only truncation mutations of RBM10, but not RBM10 mutants defective in alternative splicing activity, are observed in patients with TARP syndrome (Niceta et al, 2019).…”

“…RNA‐binding motif protein 10 (RBM10), also known as S1–1, is a member of the RNA‐binding motif gene family that regulates alternative splicing of specific pre‐mRNAs (Bechara, Sebestyén, Bernardis, Eyras, & Valcárcel, ; Inoue, Takahashi, Kimura, Watanabe, & Morisawa, ; Inoue et al, ; Loiselle & Sutherland, ; Wang et al, ). As RBM10 is located on the X chromosome, truncation mutations in the RBM10 cause a loss of function in male (Loiselle & Sutherland, ).…”

“…RNA‐binding motif protein 10 (RBM10), also known as S1–1, is a member of the RNA‐binding motif gene family that regulates alternative splicing of specific pre‐mRNAs (Bechara, Sebestyén, Bernardis, Eyras, & Valcárcel, ; Inoue, Takahashi, Kimura, Watanabe, & Morisawa, ; Inoue et al, ; Loiselle & Sutherland, ; Wang et al, ). As RBM10 is located on the X chromosome, truncation mutations in the RBM10 cause a loss of function in male (Loiselle & Sutherland, ). Deletion and frameshift mutations in the RBM10 gene have been reported to be responsible for the X chromosome‐linked disorder, named TARP (talipes equinovarus, atrial septal defect, Robin sequence and persistent left superior vena cava, MIM #311900) syndrome with pre‐ and postnatal lethality occurring in affected males (Johnston et al, ; Loiselle & Sutherland, ; Niceta et al, ), although it is not known whether loss of alternative splicing activity of RBM10 is linked to the developmental disorder.…”

“…As RBM10 is located on the X chromosome, truncation mutations in the RBM10 cause a loss of function in male (Loiselle & Sutherland, ). Deletion and frameshift mutations in the RBM10 gene have been reported to be responsible for the X chromosome‐linked disorder, named TARP (talipes equinovarus, atrial septal defect, Robin sequence and persistent left superior vena cava, MIM #311900) syndrome with pre‐ and postnatal lethality occurring in affected males (Johnston et al, ; Loiselle & Sutherland, ; Niceta et al, ), although it is not known whether loss of alternative splicing activity of RBM10 is linked to the developmental disorder. RBM10 is frequently mutated in various cancers, especially lung adenocarcinomas (LUAD) (Cancer Genome Atlas Research, ; Imielinski et al, ).…”