Genome-wide Analysis of Novel Splice Variants Induced by Topoisomerase I Poisoning Shows Preferential Occurrence in Genes Encoding Splicing Factors
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Article: Genome-wide Analysis of Novel Splice Variants Induced by Topoisomerase I Poisoning Shows Preferential Occurrence in Genes Encoding Splicing Factors
- "The AS of many RBPs and splicing factors was altered by DNA damage, including SRSF1, RBM8A, ZRANB2, SF3B3, TIA-1, and TIAL1, among others. Interestingly, in some of these cases, included exons introduced premature termination codons that could elicit nonsense-mediated mRNA decay [78,80,109]. The hSlu7 splicing factor has been suggested to hold the 5′ exon within the spliceosome complex while the correct 3' splice site is selected. "
Article: The RNA response to DNA damage[Show abstract] [Hide abstract] ABSTRACT: Multicellular organisms must ensure genome integrity to prevent accumulation of mutations, cell death, and cancer. The DNA damage response (DDR) is a complex network that senses, signals and executes multiple programs including DNA repair, cell cycle arrest, senescence and apoptosis. This entails regulation of a variety of cellular processes: DNA replication and transcription, RNA processing, mRNA translation and turnover, and post-translational modification, degradation and relocalization of proteins. Accumulated evidence over the past decades has shown that RNAs and RNA metabolism are both regulators and regulated actors of the DDR. This review aims to present a comprehensive overview of the current knowledge on the many interactions between the DNA damage and RNA fields.
- "In both cases, differential recruitment of elongation factors can also be involved. However, several studies pointed to an integrative model for kinetic coupling of splicing and transcription, where similar elongation changes could promote different splicing outcomes (Dutertre et al., 2010; Ip et al., 2011; Muñ oz et al., 2009; Solier et al., 2010). These genome-wide or multiple alternative splicing event (ASE) analyses revealed that, contrary to the simplest interpretation of the first come, first served mechanism (i.e., slow elongation causing high exon inclusion), a substantial part of the modified ASEs displayed an increase in exon skipping. "
Dataset: Mol Cell
- "Moreover, MCF7 cells are well-characterized notably in terms of their response to chemotherapeutic drugs. Our results indicate that cisplatin affects the expression level (absolute fold change >2) of more than 500 genes and provokes changes in at least 700 splicing events, thereby extending previous observations that chemotherapeutic agents affect AS [6,13,16]. This splicing reprogramming also occurs in other transformed cell lines including the breast cancer cell lines MDA-MB-231 and BT549, the endometrial adenocarcinoma cell line Ishikawa and in primary fibroblasts. "
Dataset: Gabriel et al splicing 1