RBM15

Members of the SPEN (Split-end) family of proteins, including RBM15, have repressor function in several signaling pathways and may bind to RNA through interaction with spliceosome components (Hiriart et al., 2005 [PubMed 16129689]).[supplied by OMIM

Full Name

RNA binding motif protein 15

Function

RNA-binding protein that acts as a key regulator of N6-methyladenosine (m6A) methylation of RNAs, thereby regulating different processes, such as hematopoietic cell homeostasis, alternative splicing of mRNAs and X chromosome inactivation mediated by Xist RNA (PubMed:27602518).
Associated component of the WMM complex, a complex that mediates N6-methyladenosine (m6A) methylation of RNAs, a modification that plays a role in the efficiency of mRNA splicing and RNA processing (By similarity).
Plays a key role in m6A methylation, possibly by binding target RNAs and recruiting the WMM complex (PubMed:27602518).
Involved in random X inactivation mediated by Xist RNA: acts by binding Xist RNA and recruiting the WMM complex, which mediates m6A methylation, leading to target YTHDC1 reader on Xist RNA and promoting transcription repression activity of Xist (PubMed:27602518).
Required for the development of multiple tissues, such as the maintenance of the homeostasis of long-term hematopoietic stem cells and for megakaryocyte (MK) and B-cell differentiation (By similarity).
Regulates megakaryocyte differentiation by regulating alternative splicing of genes important for megakaryocyte differentiation; probably regulates alternative splicing via m6A regulation (PubMed:26575292).
Required for placental vascular branching morphogenesis and embryonic development of the heart and spleen (By similarity).
Acts as a regulator of thrombopoietin response in hematopoietic stem cells by regulating alternative splicing of MPL (By similarity).
May also function as an mRNA export factor, stimulating export and expression of RTE-containing mRNAs which are present in many retrotransposons that require to be exported prior to splicing (PubMed:17001072, PubMed:19786495).
High affinity binding of pre-mRNA to RBM15 may allow targeting of the mRNP to the export helicase DBP5 in a manner that is independent of splicing-mediated NXF1 deposition, resulting in export prior to splicing (PubMed:17001072, PubMed:19786495).
May be implicated in HOX gene regulation (PubMed:11344311).

Biological Process

Biological Process branching involved in blood vessel morphogenesisIEA:Ensembl
Biological Process dosage compensation by inactivation of X chromosomeManual Assertion Based On ExperimentIDA:UniProtKB
Biological Process negative regulation of myeloid cell differentiationIEA:Ensembl
Biological Process placenta blood vessel developmentIEA:Ensembl
Biological Process positive regulation of transcription of Notch receptor targetIEA:Ensembl
Biological Process regulation of alternative mRNA splicing, via spliceosomeManual Assertion Based On ExperimentIDA:UniProtKB
Biological Process regulation of megakaryocyte differentiationManual Assertion Based On ExperimentIDA:UniProtKB
Biological Process RNA methylationManual Assertion Based On ExperimentIDA:UniProtKB
Biological Process spleen developmentIEA:Ensembl
Biological Process thrombopoietin-mediated signaling pathwayISS:UniProtKB
Biological Process ventricular septum morphogenesisIEA:Ensembl

Cellular Location

Nucleus speckle
Nucleus, nucleoplasm
Nucleus envelope
Nucleus membrane
Colocalizes at the nuclear pore with DBP5 and NXF1.

Involvement in disease

A chromosomal aberration involving RBM15 may be a cause of acute megakaryoblastic leukemia. Translocation t(1;22)(p13;q13) with MKL1. Although both reciprocal fusion transcripts are detected in acute megakaryoblastic leukemia (AMKL, FAB-M7), the RBM15-MKL1 chimeric protein has all the putative functional domains encoded by each gene and is the candidate oncogene.

PTM

Methylated at Arg-578 by PRMT1, leading to promote ubiquitination by CNOT4 and subsequent degradation by the proteasome.
Ubiquitinated by CNOT4 following methylation at Arg-578 by PRMT1.