RNA-binding protein 8A (RBM8A)

The protein contains 174 amino acids for an estimated molecular weight of 19889 Da.

 

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 (updated: May 8, 2019)

Protein identification was indicated in the following studies:

  1. Goodman and co-workers. (2013) The proteomics and interactomics of human erythrocytes. Exp Biol Med (Maywood) 238(5), 509-518.
  2. Lange and co-workers. (2014) Annotating N termini for the human proteome project: N termini and Nα-acetylation status differentiate stable cleaved protein species from degradation remnants in the human erythrocyte proteome. J Proteome Res. 13(4), 2028-2044.
  3. Hegedűs and co-workers. (2015) Inconsistencies in the red blood cell membrane proteome analysis: generation of a database for research and diagnostic applications. Database (Oxford) 1-8.
  4. D'Alessandro and co-workers. (2017) Red blood cell proteomics update: is there more to discover? Blood Transfus. 15(2), 182-187.

Methods

The following articles were analysed to gather the proteome content of erythrocytes.

The gene or protein list provided in the studies were processed using the ID mapping API of Uniprot in September 2018. The number of proteins identified and mapped without ambiguity in these studies is indicated below.
Only Swiss-Prot entries (reviewed) were considered for protein evidence assignation.

PublicationIdentification 1Uniprot mapping 2Not mapped /
Obsolete
TrEMBLSwiss-Prot
Goodman (2013)2289 (gene list)227853205992269
Lange (2014)123412347281224
Hegedus (2015)2638262202352387
Wilson (2016)165815281702911068
d'Alessandro (2017)18261817201815
Bryk (2017)20902060101081942
Chu (2018)18531804553621387

1 as available in the article and/or in supplementary material
2 uniprot mapping returns all protein isoforms as one entry

The compilation of older studies can be retrieved from the Red Blood Cell Collection database.

The data and differentiation stages presented below come from the proteomic study and analysis performed by our partners of the GReX consortium, more details are available in their published work.

No sequence conservation computed yet.

Interpro domains
Total structural coverage: 99%
Model score: 74

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The reference OMIM entry for this protein is 605313

Rna-binding motif protein 8a; rbm8a
Rna-binding motif protein 8; rbm8
Y14

DESCRIPTION

The RBM8A gene encodes Y14, 1 of the 4 components of the exon-junction complex (EJC), which is involved in basic cellular functions such as nuclear export and subcellular localization of specific transcripts, translational enhancement, and nonsense-mediated RNA decay (NMD) (summary by Albers et al., 2012).

CLONING

Mago nashi (MAGOH; 602603), meaning grandchildless, is the homolog of a Drosophila protein required for normal germ plasm development in fly embryos. By performing a yeast 2-hybrid screen on a fetal brain cDNA library with MAGOH as the bait, Zhao et al. (2000) recovered a cDNA encoding RBM8. The 173-amino acid RBM8 protein is more than 93% identical to the mouse and zebrafish sequences, and the mouse differences are all accounted for by an 11-amino acid N-terminal insertion and another single-residue insertion in the mouse sequence. Exchange partner and GST pull-down assays confirmed the MAGOH-RBM8 interaction and showed that RBM8 is expressed as a 26-kD protein, slightly larger than the predicted mass of 23 kD. Northern blot analysis detected a major RBM8 transcript of less than 1.0 kb in all tissues tested, with weakest expression in pancreas and brain. By searching an EST database for homologs of the gonadotropin-releasing hormone receptor (GNRHR; 138850), followed by 5-prime RACE on a skeletal muscle cDNA library, Conklin et al. (2000) identified a cDNA encoding RBM8. Northern blot analysis detected a major 0.9-kb transcript in all tissues tested. Sequence analysis of the 174-amino acid protein predicted an RNA-binding domain, which is composed of 2 amphipathic alpha helices packed against a 4-stranded beta sheet, and a C-terminal arg-rich segment. By performing a yeast 2-hybrid screen on a HeLa cell cDNA library to identify potential cargoes for RAN-binding protein-5 (RANBP5; 602008), Kataoka et al. (2000) isolated cDNAs encoding RBM8, which they called Y14. RBM8 encodes a predicted 174-amino acid, predominantly nuclear nucleocytoplasmic shuttling protein. Salicioni et al. (2000) used a yeast 2-hybrid screen to identify cDNAs from a human fetal brain cDNA library encoding proteins that interact with OVCA1 (603527), a candidate tumor suppressor protein. They identified cDNAs, which they initially referred to as BOV1, that appeared to encode a new member of the conserved RNA-binding motif protein family. One of the cDNAs isolated was identical to RBM8A; another, designated RBM8B, was thought by Salicioni et al. (2000) to be a novel functional gene, but was later determined to be a pseudogene. Northern blot analysis revealed that BOV1 is ubiquitously expressed as 3 distinct mRNA species of 1, 3.2, and 5.8 kb.

GENE FUNCTION

Kataoka et al. (2000) found that RBM8 associates preferentially with mRNAs produced by splicing and not with pre-mRNAs, introns, or mRNAs produced from intronless cDNAs. RBM8 associates with both nuclear mRNAs and newly exported cytoplasmic mRNAs. Splicing of a single intron is sufficient for RBM8 association. RBM8-containing nuclear complexes are different from general heterogeneous nuclear ribonucleoprotein (hnRNP) complexes in that they contain hnRNP proteins and several unique proteins, including the mRNA export factor TAP (NXF1; 602647). Thus, RBM8 defines novel intermediates in the pathway of gene expression, postsplicing nuclear preexport mRNPs, and newly exported cytoplasmic mRNPs, whose composition is established by splicing. These findings suggested th ... More on the omim web site

Subscribe to this protein entry history

May 11, 2019: Protein entry updated
Automatic update: Entry updated from uniprot information.

Feb. 10, 2018: Protein entry updated
Automatic update: Entry updated from uniprot information.

Feb. 2, 2018: Protein entry updated
Automatic update: Uniprot description updated

Dec. 19, 2017: Protein entry updated
Automatic update: Uniprot description updated

June 20, 2017: Protein entry updated
Automatic update: comparative model was added.

March 16, 2016: Protein entry updated
Automatic update: OMIM entry 605313 was added.

Feb. 24, 2016: Protein entry updated
Automatic update: model status changed