Alternative splicing is normal in eukaryotes. It greatly increases the diversity of proteins that can be encoded by the genome. In humans, ~95% of multiexonic genes are alternatively spliced.
There are various kinds of alternative splicing: the most common is exon skipping. An exon may be included in mRNAs under some conditions or in particular tissues, and omitted from the mRNA in others. There are splicing activators that promote the use of a particular splice site, and splicing repressors that reduce the use of a particular site. New types of alternative splicing are being found.
Abnormal variations in splicing occur in disease. Many human genetic disorders come from splicing variants. Abnormal splicing variants may also contribute to the development of cancer. Non-working splicing products are usually dealt with by post-transcriptional quality control. That is, they are chopped up by enzymes.
Source of diversityEdit
Alternative splicing (the re-combination of different exons) is a major source of genetic diversity in eukaryotes. One particular Drosophila gene (DSCAM) can be alternatively spliced into 38,000 different mRNA.
- Black, Douglas L. (2003). "Mechanisms of alternative pre-messenger RNA splicing". Annual Reviews of Biochemistry 72 (1): 291–336. doi:10.1146/annurev.biochem.72.121801.161720. PMID 12626338.
- multiexonic: those genes where the coding sections (exons) are separated by non-coding sections (introns)
- Pan, Q et al. (2008). "Deep surveying of alternative splicing complexity in the human transcriptome by high-throughput sequencing". Nature Genetics 40 (12): 1413–1415. doi:10.1038/ng.259. PMID 18978789.
- Matlin, AJ; Clark F, Smith CWJ (2005). "Understanding alternative splicing: towards a cellular code". Nature Reviews 6 (5): 386–398. doi:10.1038/nrm1645. PMID 15956978.
- David, C.J.; Manley, J.L. (2008). "The search for alternative splicing regulators: new approaches offer a path to a splicing code". Genes & Development 22 (3): 279. doi:10.1101/gad.1643108. PMID 18245441.
- Skotheim R.I. and Nees M (2007). "Alternative splicing in cancer: noise, functional, or systematic?". The international journal of biochemistry & cell biology 39 (7-8): 1432–49. doi:10.1016/j.biocel.2007.02.016. PMID 17416541.
- Bauer, Joseph Alan et al. (2009). "A global view of cancer-specific transcript variants by subtractive transcriptome-wide analysis". PLoS ONE 4 (3): e4732. doi:10.1371/journal.pone.0004732. PMC 2648985. PMID 19266097.
- Fackenthal J; Godley L (2008). "Aberrant RNA splicing and its functional consequences in cancer cells" (Free full text). Disease models & mechanisms 1 (1): 37–42. doi:10.1242/dmm.000331. PMC 2561970. PMID 19048051.
- Danckwardt S et al. (2002). "Abnormally spliced beta-globin mRNAs: a single point mutation generates transcripts sensitive and insensitive to nonsense-mediated mRNA decay". Blood 99 (5): 1811–6. doi:10.1182/blood.V99.5.1811. PMID 11861299. http://bloodjournal.hematologylibrary.org/cgi/content/full/99/5/1811.
- Schmucker D. et al. (2000). "Drosophila Dscam is an axon guidance receptor exhibiting extraordinary molecular diversity". Cell 101 (6): 671–684. doi:10.1016/S0092-8674(00)80878-8. PMID 10892653.