Editing Alternative splicing (section)

==Modes==
[[File:Alt splicing bestiary2.jpg|left|thumb|Traditional classification of basic types of alternative RNA splicing events. Exons are represented as blue and yellow blocks, introns as lines in between.]]
[[File:Splice types frequency.jpg|right|thumb|Relative frequencies of types of alternative splicing events differ between humans and fruit flies.<ref name=Sammeth/>]]Five basic modes of alternative splicing are generally recognized.<ref name=Black/><ref name=Pan2008>{{cite journal | vauthors = Pan Q, Shai O, Lee LJ, Frey BJ, Blencowe BJ | title = Deep surveying of alternative splicing complexity in the human transcriptome by high-throughput sequencing | journal = Nature Genetics | volume = 40 | issue = 12 | pages = 1413–5 | date = December 2008 | pmid = 18978789 | doi = 10.1038/ng.259 | s2cid = 9228930 }}</ref><ref name=Matlin>{{cite journal | vauthors = Matlin AJ, Clark F, Smith CW | title = Understanding alternative splicing: towards a cellular code | journal = Nature Reviews. Molecular Cell Biology | volume = 6 | issue = 5 | pages = 386–98 | date = May 2005 | pmid = 15956978 | doi = 10.1038/nrm1645 | s2cid = 14883495 }}</ref><ref name=Sammeth>
{{cite journal | vauthors = Sammeth M, Foissac S, Guigó R | title = A general definition and nomenclature for alternative splicing events | journal = PLOS Computational Biology | volume = 4 | issue = 8 | pages = e1000147 | date = August 2008 | pmid = 18688268 | pmc = 2467475 | doi = 10.1371/journal.pcbi.1000147 | veditors = Brent MR | bibcode = 2008PLSCB...4E0147S | doi-access = free }}</ref>
* '''Exon skipping''' or '''cassette exon''': in this case, an [[exon]] may be spliced out of the primary [[Transcription (genetics)|transcript]] or retained. This is the most common mode in mammalian [[pre-mRNA]]s.<ref name=Sammeth/>
* '''Mutually exclusive exons''': One of two exons is retained in mRNAs after splicing, but not both.
* '''Alternative donor site''': An alternative 5' splice junction (donor site) is used, changing the 3' boundary of the [[Upstream transcription factor|upstream]] exon.
* '''Alternative acceptor site''': An alternative 3' splice junction (acceptor site) is used, changing the 5' boundary of the downstream exon.
* '''Intron retention''': A sequence may be spliced out as an intron or simply retained. This is distinguished from exon skipping because the retained sequence is not flanked by [[introns]]. If the retained intron is in the coding region, the intron must encode amino acids in frame with the neighboring exons, or a stop codon or a shift in the [[reading frame]] will cause the protein to be non-functional. This is the rarest mode in mammals but the most common in plants.<ref name=Sammeth/><ref>{{Cite journal|last1=Ner-Gaon|first1=Hadas|last2=Halachmi|first2=Ronit|last3=Savaldi-Goldstein|first3=Sigal|last4=Rubin|first4=Eitan|last5=Ophir|first5=Ron|last6=Fluhr|first6=Robert|date=2004|title=Intron retention is a major phenomenon in alternative splicing in Arabidopsis|journal=The Plant Journal|language=en|volume=39|issue=6|pages=877–885|doi=10.1111/j.1365-313X.2004.02172.x|pmid=15341630|issn=1365-313X|doi-access=free}}</ref>

In addition to these primary modes of alternative splicing, there are two other main mechanisms by which different mRNAs may be generated from the same gene; multiple [[Promoter (biology)|promoter]]s and multiple [[polyadenylation]] sites. Use of multiple promoters is properly described as a [[transcriptional regulation]] mechanism rather than alternative splicing; by starting transcription at different points, transcripts with different 5'-most exons can be generated. At the other end, multiple polyadenylation sites provide different 3' end points for the transcript. Both of these mechanisms are found in combination with alternative splicing and provide additional variety in mRNAs derived from a gene.<ref name=Black/><ref name=Matlin/> [[File:Hyaluronidase3.gif|right|thumb|Schematic cutoff from 3 splicing structures in the murine [[hyaluronidase]] gene. Directionality of transcription from 5' to 3' is shown from left to right. Exons and introns are not drawn to scale.]]

<br>These modes describe basic splicing mechanisms, but may be inadequate to describe complex splicing events. For instance, the figure to the right shows 3 spliceforms from the mouse [[hyaluronidase]] 3 gene. Comparing the exonic structure shown in the first line (green) with the one in the second line (yellow) shows intron retention, whereas the comparison between the second and the third spliceform (yellow vs. blue) exhibits exon skipping. A model nomenclature to uniquely designate all possible splicing patterns has recently been proposed.<ref name=Sammeth/>