Journal article
Human Inositol Polyphosphate Multikinase Regulates Transcript-Selective Nuclear mRNA Export to Preserve Genome Integrity
VO Wickramasinghe, JM Savill, S Chavali, AB Jonsdottir, E Rajendra, T Grüner, RA Laskey, MM Babu, AR Venkitaraman
Molecular Cell | CELL PRESS | Published : 2013
Abstract
Messenger RNA (mRNA) export from the nucleus is essential for eukaryotic gene expression. Here we identify a transcript-selective nuclear export mechanism affecting certain human transcripts, enriched for functions in genome duplication and repair, controlled by inositol polyphosphate multikinase (IPMK), an enzyme catalyzing inositol polyphosphate and phosphoinositide turnover. We studied transcripts encoding RAD51, a protein essential for DNA repair by homologous recombination (HR), to characterize the mechanism underlying IPMK-regulated mRNA export. IPMK depletion or catalytic inactivation selectively decreases RAD51 protein abundance and the nuclear export of RAD51 mRNA, thereby impairing..
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Awarded by European Molecular Biology Organization
Funding Acknowledgements
We thank Prof. Robin Irvine (University of Cambridge) and members of the Venkitaraman laboratory for helpful discussions and Anand Jeyasekharan for technical assistance. J.M.S. was supported by a UK Medical Research Council (MRC) studentship to A. R. V. This work was supported by the Medical Research Council (S. C. and M. M. B.), HFSP (RGY0073/2010, M. M. B.), EMBO (Young Investigator Program, M. M. B.; Long-Term Fellowship, S. C.), and ERASysBio+ (GRAPPLE, S. C. and M. M. B.). This work was also supported by grants to A. R. V. from the European Union (FP7 TRIREME, supporting A.B.J. and T. G.) and the MRC (supporting V.O.W. and E. R.). V.O.W., J.M.S., A.B.J., T. G., and A. R. V. conceived of and performed the experiments reported in this paper. E. R. performed structural analyses of IPMK and homologous proteins to identify mutations impairing catalysis. S. C. and M. M. B. performed statistical analyses of mRNA motifs. A. R. V. wrote the paper, with assistance from V.O.W. and J.M.S.