Editing Alternative splicing (section)

===General splicing mechanism===
{{Main|RNA splicing}}
[[File:A complex.jpg|thumb|Spliceosome A complex defines the 5' and 3' ends of the intron before removal<ref name=Matlin/>]]
When the pre-mRNA has been transcribed from the [[DNA]], it includes several [[intron]]s and [[exon]]s. (In [[nematode]]s, the mean is 4–5 exons and introns; in the fruit fly ''[[Drosophila melanogaster|Drosophila]]'' there can be more than 100 introns and exons in one transcribed pre-mRNA.) The exons to be retained in the [[mRNA]] are determined during the splicing process. The regulation and selection of splice sites are done by trans-acting splicing activator and splicing repressor proteins as well as cis-acting elements within the pre-mRNA itself such as exonic splicing enhancers and exonic splicing silencers.

The typical eukaryotic nuclear intron has consensus sequences defining important regions. Each intron has the sequence GU at its 5' end. Near the 3' end there is a branch site. The nucleotide at the branchpoint is always an A; the consensus around this sequence varies somewhat. In humans the branch site consensus sequence is yUnAy.<ref name=Gao>{{cite journal | vauthors = Gao K, Masuda A, Matsuura T, Ohno K | title = Human branch point consensus sequence is yUnAy | journal = Nucleic Acids Research | volume = 36 | issue = 7 | pages = 2257–67 | date = April 2008 | pmid = 18285363 | pmc = 2367711 | doi = 10.1093/nar/gkn073 }}</ref> The branch site is followed by a series of [[pyrimidine]]s – the [[polypyrimidine tract]] – then by AG at the 3' end.<ref name=Matlin/>

Splicing of mRNA is performed by an RNA and protein complex known as the [[spliceosome]], containing [[snRNP]]s designated U1, [[U2]], U4, U5, and U6 (U3 is not involved in mRNA splicing).<ref name=Clark>{{cite book | vauthors = Clark D |title=Molecular biology |publisher=Elsevier Academic Press |location=Amsterdam |year=2005 |isbn=978-0-12-175551-5}}</ref> U1 binds to the 5' GU and U2, with the assistance of the [[U2AF2|U2AF]] protein factors, binds to the branchpoint A within the branch site. The complex at this stage is known as the spliceosome A complex. Formation of the A complex is usually the key step in determining the ends of the intron to be spliced out, and defining the ends of the exon to be retained.<ref name=Matlin/> (The U nomenclature derives from their high uridine content).

The U4,U5,U6 complex binds, and U6 replaces the U1 position. U1 and U4 leave. The remaining complex then performs two [[transesterification]] reactions. In the first transesterification, 5' end of the intron is cleaved from the upstream exon and joined to the branch site A by a 2',5'-[[phosphodiester]] linkage. In the second transesterification, the 3' end of the intron is cleaved from the downstream exon, and the two exons are joined by a phosphodiester bond. The intron is then released in lariat form and degraded.<ref name=Black>{{cite journal | vauthors = Black DL | title = Mechanisms of alternative pre-messenger RNA splicing | journal = Annual Review of Biochemistry | volume = 72 | issue = 1 | pages = 291–336 | year = 2003 | pmid = 12626338 | doi = 10.1146/annurev.biochem.72.121801.161720 | s2cid = 23576288 | url = https://cloudfront.escholarship.org/dist/prd/content/qt2hg605wm/qt2hg605wm.pdf }}</ref>