title: A novel functional role for MMSET in RNA processing based on the link between the REIIBP isoform and its interaction with the SMN complex.
abstract: The chromosomal translocation t(4;14) deregulates MMSET (WHSC1/NSD2) expression and is a poor prognostic factor in multiple myeloma (MM). MMSET encodes two major protein isoforms. We have characterized the role of the shorter isoform (REIIBP) in myeloma cells and identified a clear and novel interaction of REIIBP with members of the SMN (survival of motor neuron) complex that directly affects the assembly of the spliceosomal ribonucleic particles. Using RNA-seq we show that REIIBP influences the RNA splicing pattern of the cell. This new discovery provides novel insights into the understanding of MM pathology, and potential new leads for therapeutic targeting.
authors.affiliation: Centre for Myeloma Research, Division of Molecular Pathology, The Institute of Cancer Research, Sutton, United Kingdom.
authors.forename: Fabio
authors.initials: F
authors.lastname: Mirabella
authors.affiliation: Centre for Myeloma Research, Division of Molecular Pathology, The Institute of Cancer Research, Sutton, United Kingdom.
authors.forename: Alexander
authors.initials: A
authors.lastname: Murison
authors.affiliation: Centre for Myeloma Research, Division of Molecular Pathology, The Institute of Cancer Research, Sutton, United Kingdom.
authors.forename: Lauren I
authors.initials: LI
authors.lastname: Aronson
authors.affiliation: Centre for Myeloma Research, Division of Molecular Pathology, The Institute of Cancer Research, Sutton, United Kingdom.
authors.forename: Christopher P
authors.initials: CP
authors.lastname: Wardell
authors.affiliation: Proteomics Core Facility, The Institute of Cancer Research, London, United Kingdom.
authors.forename: Andrew J
authors.initials: AJ
authors.lastname: Thompson
authors.affiliation: Proteomics Core Facility, The Institute of Cancer Research, London, United Kingdom.
authors.forename: Sarah J
authors.initials: SJ
authors.lastname: Hanrahan
authors.affiliation: Centre for Myeloma Research, Division of Molecular Pathology, The Institute of Cancer Research, Sutton, United Kingdom.
authors.forename: Jacqueline H L
authors.initials: JH
authors.lastname: Fok
authors.affiliation: Centre for Myeloma Research, Division of Molecular Pathology, The Institute of Cancer Research, Sutton, United Kingdom.
authors.forename: Charlotte
authors.initials: C
authors.lastname: Pawlyn
authors.affiliation: Centre for Myeloma Research, Division of Molecular Pathology, The Institute of Cancer Research, Sutton, United Kingdom.
authors.forename: Martin F
authors.initials: MF
authors.lastname: Kaiser
authors.affiliation: Centre for Myeloma Research, Division of Molecular Pathology, The Institute of Cancer Research, Sutton, United Kingdom.
authors.forename: Brian A
authors.initials: BA
authors.lastname: Walker
authors.affiliation: Centre for Myeloma Research, Division of Molecular Pathology, The Institute of Cancer Research, Sutton, United Kingdom.
authors.forename: Faith E
authors.initials: FE
authors.lastname: Davies
authors.affiliation: Centre for Myeloma Research, Division of Molecular Pathology, The Institute of Cancer Research, Sutton, United Kingdom.
authors.forename: Gareth J
authors.initials: GJ
authors.lastname: Morgan
mesh_terms: D049109:Cell Proliferation; D002883:Chromosomes, Human, Pair 14 / Q000235:genetics; D002894:Chromosomes, Human, Pair 4 / Q000235:genetics; D006367:HeLa Cells; D011495:Histone-Lysine N-Methyltransferase / Q000378:metabolism*; D006657:Histones / Q000378:metabolism; D006801:Humans; D007438:Introns / Q000235:genetics; D013058:Mass Spectrometry; D008745:Methylation; D009101:Multiple Myeloma / Q000235:genetics / Q000473:pathology; D010641:Phenotype; D011485:Protein Binding; D020033:Protein Isoforms / Q000378:metabolism; D017434:Protein Structure, Tertiary; D012323:RNA Processing, Post-Transcriptional; D012326:RNA Splicing / Q000235:genetics; D012097:Repressor Proteins / Q000378:metabolism*; D017411:Ribonucleoproteins, Small Nuclear / Q000378:metabolism; D055532:SMN Complex Proteins / Q000378:metabolism*; D017381:Spliceosomes / Q000378:metabolism; D014178:Translocation, Genetic
chemical_list: D006657:Histones; D020033:Protein Isoforms; D012097:Repressor Proteins; D017411:Ribonucleoproteins, Small Nuclear; D055532:SMN Complex Proteins; D011495:Histone-Lysine N-Methyltransferase; C419586:NSD2 protein, human