Selective control of genome maintenance pathways by RNA processing factors
Before messenger RNA can be translated into protein, it must be processed and spliced into a mature transcript, and then exported from sites of transcription and processing in the nucleus to the cytoplasm1. It is emerging that the pathways which process newly transcribed RNA also regulate the response to DNA damage at multiple levels2. I will discuss recent insights that highlight the unexpectedly intimate involvement of RNA processing pathways in the maintenance of genome stability3, 4. The importance of these pathways is underscored by the growing appreciation that defects in these regulatory connections may be connected to the genome instability involved in several human diseases, including cancer.
Dr. Wickramasinghe is currently at the University of Cambridge but will move in June 2016 to head up the newly formed RNA Biology and Cancer laboratory at the Peter Mac Callum Cancer Centre.
1. Wickramasinghe, V.O. & Laskey, R.A. Control of mammalian gene expression by selective mRNA export. Nat Rev Mol Cell Biol 16, 431-42 (2015).
2. Wickramasinghe, V.O. & Venkitaraman, A.R. RNA processing and genome stability: cause and consequence Mol Cell (2016).
3. Wickramasinghe, V.O. et al. Regulation of constitutive and alternative mRNA splicing across the human transcriptome by PRPF8 is determined by 5’ splice site strength. Genome Biol 16, 201 (2015).
4. Wickramasinghe, V.O. et al. Human inositol polyphosphate multikinase regulates transcript-selective nuclear mRNA export to preserve genome integrity. Mol Cell 51, 737-50 (2013).
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