Connecting the dots: chromatin and alternative splicing in EMT.
Nature has devised sophisticated cellular machinery to process mRNA transcripts produced by RNA Polymerase II, removing intronic regions and connecting exons together, to produce mature RNAs. This process, known as splicing, is very closely linked to transcription. Alternative splicing, or the ability to produce different combinations of exons that are spliced together from the same genomic template, is a fundamental means of regulating protein complexity. Similar to transcription, both constitutive and alternative splicing can be regulated by chromatin and its associated factors in response to various signal transduction pathways activated by external stimuli. This regulation can vary between different cell types, and interference with these pathways can lead to changes in splicing, often resulting in aberrant cellular states and disease. The epithelial to mesenchymal transition (EMT), which leads to cancer metastasis, is influenced by alternative splicing events of chromatin remodelers and epigenetic factors such as DNA methylation and non-coding RNAs. In this review, we will discuss the role of epigenetic factors including chromatin, chromatin remodelers, DNA methyltransferases, and microRNAs in the context of alternative splicing, and discuss their potential involvement in alternative splicing during the EMT process.
a Department of Basic Sciences, University of North Dakota School of Medicine and Health Sciences, 501 N. Columbia Road Stop 9061, Grand Forks, ND 58202-9061, USA.
Jessica A
JA
Warns
b Children's Hospital Research Institute of Manitoba, John Buhler Research Centre, Winnipeg, Manitoba R3E 3P4, Canada.
James R
JR
Davie
a Department of Basic Sciences, University of North Dakota School of Medicine and Health Sciences, 501 N. Columbia Road Stop 9061, Grand Forks, ND 58202-9061, USA.
Archana
A
Dhasarathy
D017398:Alternative Splicing; D002843:Chromatin / Q000378:metabolism*; D042002:Chromatin Assembly and Disassembly; D019175:DNA Methylation; D058750:Epithelial-Mesenchymal Transition / Q000235:genetics*; D005091:Exons; D042421:Histone Code; D006801:Humans; D007438:Introns; D009369:Neoplasms / Q000737:chemistry / Q000235:genetics*; D009707:Nucleosomes / Q000378:metabolism*; D012319:RNA Polymerase II / Q000378:metabolism; D012322:RNA Precursors / Q000737:chemistry* / Q000235:genetics; D012333:RNA, Messenger / Q000235:genetics; D022661:RNA, Untranslated / Q000737:chemistry / Q000235:genetics; D015398:Signal Transduction; D014158:Transcription, Genetic
D002843:Chromatin; D009707:Nucleosomes; D012322:RNA Precursors; D012333:RNA, Messenger; D022661:RNA, Untranslated; D012319:RNA Polymerase II
EMT; TEM; alternative splicing; cancer; chromatin; chromatine; epigenetics; épigénétique; épissage alternatif