RBM8A
Function
Required for pre-mRNA splicing as component of the spliceosome (PubMed:28502770, PubMed:29301961). Core component of the splicing-dependent multiprotein exon junction complex (EJC) deposited at splice junctions on mRNAs. The EJC is a dynamic structure consisting of core proteins and several peripheral nuclear and cytoplasmic associated factors that join the complex only transiently either during EJC assembly or during subsequent mRNA metabolism. The EJC marks the position of the exon-exon junction in the mature mRNA for the gene expression machinery and the core components remain bound to spliced mRNAs throughout all stages of mRNA metabolism thereby influencing downstream processes including nuclear mRNA export, subcellular mRNA localization, translation efficiency and nonsense-mediated mRNA decay (NMD). The MAGOH-RBM8A heterodimer inhibits the ATPase activity of EIF4A3, thereby trapping the ATP-bound EJC core onto spliced mRNA in a stable conformation. The MAGOH-RBM8A heterodimer interacts with the EJC key regulator PYM1 leading to EJC disassembly in the cytoplasm and translation enhancement of EJC-bearing spliced mRNAs by recruiting them to the ribosomal 48S preinitiation complex. Its removal from cytoplasmic mRNAs requires translation initiation from EJC-bearing spliced mRNAs. Associates preferentially with mRNAs produced by splicing. Does not interact with pre-mRNAs, introns, or mRNAs produced from intronless cDNAs. Associates with both nuclear mRNAs and newly exported cytoplasmic mRNAs. The MAGOH-RBM8A heterodimer is a component of the nonsense mediated decay (NMD) pathway. Involved in the splicing modulation of BCL2L1/Bcl-X (and probably other apoptotic genes); specifically inhibits formation of proapoptotic isoforms such as Bcl-X(S); the function is different from the established EJC assembly.
Involvement in disease
Thrombocytopenia-absent radius syndrome
TAR
An autosomal recessive disorder characterized by bilateral absence of the radii with the presence of both thumbs, thrombocytopenia, low numbers of megakaryocytes, and bleeding episodes in the first year of life. Thrombocytopenic episodes decrease with age. Skeletal anomalies range from absence of radii to virtual absence of upper limbs, with or without lower limb defects such as malformations of the hip and knee.
None
The disease is caused by variants affecting the gene represented in this entry.
Sequence Similarities
Belongs to the RBM8A family.
Tissue Specificity
Ubiquitous.
Cellular localization
- Nucleus
- Nucleus speckle
- Cytoplasm
- Nucleocytoplasmic shuttling protein (PubMed:11030346). Travels to the cytoplasm as part of the exon junction complex (EJC) bound to mRNA. Colocalizes with the core EJC, ALYREF/THOC4, NXF1 and UAP56 in the nucleus and nuclear speckles (PubMed:19324961).
Alternative names
RBM8, HSPC114, MDS014, RBM8A, RNA-binding protein 8A, Binder of OVCA1-1, RNA-binding motif protein 8A, RNA-binding protein Y14, Ribonucleoprotein RBM8A, BOV-1