7z27

Structural highlights

Disease

RBM15_HUMAN Megakaryoblastic acute myeloid leukemia with t(1;22)(p13;q13). 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.^{[1] [2]}

Function

RBM15_HUMAN 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).[UniProtKB:Q0VBL3]^{[3] [4] [5] [6] [7]}

References

1. ↑ Mercher T, Coniat MB, Monni R, Mauchauffe M, Nguyen Khac F, Gressin L, Mugneret F, Leblanc T, Dastugue N, Berger R, Bernard OA. Involvement of a human gene related to the Drosophila spen gene in the recurrent t(1;22) translocation of acute megakaryocytic leukemia. Proc Natl Acad Sci U S A. 2001 May 8;98(10):5776-9. doi: 10.1073/pnas.101001498. PMID:11344311 doi:http://dx.doi.org/10.1073/pnas.101001498
2. ↑ Ma Z, Morris SW, Valentine V, Li M, Herbrick JA, Cui X, Bouman D, Li Y, Mehta PK, Nizetic D, Kaneko Y, Chan GC, Chan LC, Squire J, Scherer SW, Hitzler JK. Fusion of two novel genes, RBM15 and MKL1, in the t(1;22)(p13;q13) of acute megakaryoblastic leukemia. Nat Genet. 2001 Jul;28(3):220-1. doi: 10.1038/90054. PMID:11431691 doi:http://dx.doi.org/10.1038/90054
3. ↑ Lindtner S, Zolotukhin AS, Uranishi H, Bear J, Kulkarni V, Smulevitch S, Samiotaki M, Panayotou G, Felber BK, Pavlakis GN. RNA-binding motif protein 15 binds to the RNA transport element RTE and provides a direct link to the NXF1 export pathway. J Biol Chem. 2006 Dec 1;281(48):36915-28. doi: 10.1074/jbc.M608745200. Epub 2006 , Sep 25. PMID:17001072 doi:http://dx.doi.org/10.1074/jbc.M608745200
4. ↑ Zolotukhin AS, Uranishi H, Lindtner S, Bear J, Pavlakis GN, Felber BK. Nuclear export factor RBM15 facilitates the access of DBP5 to mRNA. Nucleic Acids Res. 2009 Nov;37(21):7151-62. Epub . PMID:19786495 doi:http://dx.doi.org/gkp782
5. ↑ Zhang L, Tran NT, Su H, Wang R, Lu Y, Tang H, Aoyagi S, Guo A, Khodadadi-Jamayran A, Zhou D, Qian K, Hricik T, Cote J, Han X, Zhou W, Laha S, Abdel-Wahab O, Levine RL, Raffel G, Liu Y, Chen D, Li H, Townes T, Wang H, Deng H, Zheng YG, Leslie C, Luo M, Zhao X. Cross-talk between PRMT1-mediated methylation and ubiquitylation on RBM15 controls RNA splicing. Elife. 2015 Nov 17;4. pii: 07938. doi: 10.7554/eLife.07938. PMID:26575292 doi:http://dx.doi.org/10.7554/eLife.07938
6. ↑ Patil DP, Chen CK, Pickering BF, Chow A, Jackson C, Guttman M, Jaffrey SR. m(6)A RNA methylation promotes XIST-mediated transcriptional repression. Nature. 2016 Sep 15;537(7620):369-373. doi: 10.1038/nature19342. Epub 2016 Sep 7. PMID:27602518 doi:http://dx.doi.org/10.1038/nature19342
7. ↑ Mercher T, Coniat MB, Monni R, Mauchauffe M, Nguyen Khac F, Gressin L, Mugneret F, Leblanc T, Dastugue N, Berger R, Bernard OA. Involvement of a human gene related to the Drosophila spen gene in the recurrent t(1;22) translocation of acute megakaryocytic leukemia. Proc Natl Acad Sci U S A. 2001 May 8;98(10):5776-9. doi: 10.1073/pnas.101001498. PMID:11344311 doi:http://dx.doi.org/10.1073/pnas.101001498