DNA damage affects splicing factors by altering their post-translational modification, localization, expression and activity. Furthermore, DNA damage often disrupts splicing by interfering with its coupling to transcription. DNA damage also has an impact on the splicing and alternative splicing of genes intimately associated with DNA repair. For instance, DNA damages modulate the alternative splicing of the DNA repair genes Brca1 and Ercc1. Experimental manipulation of splicing Splicing events can be experimentally altered by binding steric-blocking antisense oligos, such as Morpholinos or Peptide nucleic acids to snRNP binding sites, to the branchpoint nucleotide that closes the lariat, or to splice-regulatory element binding sites. Splicing errors and variation It has been suggested that one third of all disease-causing mutations impact on splicing. Common errors include: Mutation of a splice site resulting in loss of function of that site. Results in exposure of a premature stop codon, loss of an exon, or inclusion of an intron. Mutation of a splice site reducing specificity. May result in variation in the splice location, causing insertion or deletion of amino acids, or most likely, a disruption of the reading frame. Displacement of a splice site, leading to inclusion or exclusion of more RNA than expected, resulting in longer or shorter exons. Although many splicing errors are safeguarded by a cellular quality control mechanism termed nonsense-mediated mRNA decay (NMD), a number of splicing-related diseases also exist, as suggested above. Allelic differences in mRNA splicing are likely to be a common and important source of phenotypic diversity at the molecular level, in addition to their contribution to genetic disease susceptibility. Indeed, genome-wide studies in humans have identified a range of genes that are subject to allele-specific splicing. In plants, variation for flooding stress tolerance correlated with stress-induced alternative splicing of transcripts associated with gluconeogenesis and other processes. Protein splicing In addition to RNA, proteins can undergo splicing. Although the biomolecular mechanisms are different, the principle is the same: parts of the protein, called inteins instead of introns, are removed. The remaining parts, called exteins instead of exons, are fused together. Protein splicing has been observed in a wide range of organisms, including bacteria, archaea, plants, yeast and humans. See also cDNA DBASS3/5 Exon junction complex mRNA capping Polyadenylation Post-transcriptional modification RNA editing SWAP protein domain, a splicing regulator References External links Virtual Cell Animation Collection: mRNA Splicing Gene expression Spliceosome