A novel functional role for MMSET in RNA processing based on the link between the REIIBP isoform and its interaction with the SMN complex

Fabio Mirabella; Alexander Murison; Lauren I Aronson; Christopher P Wardell; Andrew J Thompson; Sarah J Hanrahan; Jacqueline H L Fok; Charlotte Pawlyn; Martin F Kaiser; Brian A Walker; Faith E Davies; Gareth J Morgan

doi:10.1371/journal.pone.0099493

A novel functional role for MMSET in RNA processing based on the link between the REIIBP isoform and its interaction with the SMN complex

PLoS One. 2014 Jun 12;9(6):e99493. doi: 10.1371/journal.pone.0099493. eCollection 2014.

Affiliations

¹ Centre for Myeloma Research, Division of Molecular Pathology, The Institute of Cancer Research, Sutton, United Kingdom.
² Proteomics Core Facility, The Institute of Cancer Research, London, United Kingdom.

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.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Cell Proliferation
Chromosomes, Human, Pair 14 / genetics
Chromosomes, Human, Pair 4 / genetics
HeLa Cells
Histone-Lysine N-Methyltransferase / metabolism*
Histones / metabolism
Humans
Introns / genetics
Mass Spectrometry
Methylation
Multiple Myeloma / genetics
Multiple Myeloma / pathology
Phenotype
Protein Binding
Protein Isoforms / metabolism
Protein Structure, Tertiary
RNA Processing, Post-Transcriptional*
RNA Splicing / genetics
Repressor Proteins / metabolism*
Ribonucleoproteins, Small Nuclear / metabolism
SMN Complex Proteins / metabolism*
Spliceosomes / metabolism
Translocation, Genetic

Substances

Histones
Protein Isoforms
Repressor Proteins
Ribonucleoproteins, Small Nuclear
SMN Complex Proteins
Histone-Lysine N-Methyltransferase
NSD2 protein, human

Grants and funding

This work was supported by a programme grant from Myeloma UK [MUK005X] (http://www.myeloma.org.uk/) and funding from The NIHR Biomedical Research Centre at the Royal Marsden Hospital. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.