The discovery of an increasing number of alternative splicing events in the human genome highlighted that ∼94% of genes generate alternatively spliced transcripts that may produce different protein isoforms with diverse functions. It is now well known that several diseases are a direct and indirect consequence of aberrant splicing events in humans. In addition to the conventional mode of alternative splicing regulation by ‘cis’ RNA-binding sites and ‘trans’ RNA-binding proteins, recent literature provides enormous evidence for epigenetic regulation of alternative splicing. The epigenetic modifications may regulate alternative splicing by either influencing the transcription elongation rate of RNA polymerase II or by recruiting a specific splicing regulator via different chromatin adaptors. The epigenetic alterations and aberrant alternative splicing are known to be associated with various diseases individually, but this review discusses/highlights the latest literature on the role of epigenetic alterations in the regulation of alternative splicing and thereby cancer progression. This review also points out the need for further studies to understand the interplay between epigenetic modifications and aberrant alternative splicing in cancer progression.
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Cover Image
Cover Image
The interfacial active site of the type IB GTP cyclohydrolase from Neisseria gonorrhoeae (grey and green ribbons), in complex with zinc (magenta ball) and the reaction intermediate analog and potent inhibitor 8-oxo-GTP (stick model). The structure sheds light on the complex and unique catalytic strategy of this potential antibacterial target, and offers a starting point for the design of specific inhibitors against the enzyme. For more information, please see study by Paranagama et al. in this issue, pages 1017–1039. Image provided by Manal Swairjo.
A saga of cancer epigenetics: linking epigenetics to alternative splicing
Sathiya Pandi Narayanan, Smriti Singh, Sanjeev Shukla; A saga of cancer epigenetics: linking epigenetics to alternative splicing. Biochem J 15 March 2017; 474 (6): 885–896. doi: https://doi.org/10.1042/BCJ20161047
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