Editing RNA splicing (section)

====Formation and activity====
Splicing is catalyzed by the [[spliceosome]], a large RNA-protein complex composed of five small nuclear ribonucleoproteins ([[snRNP]]s).  Assembly and activity of the spliceosome occurs during transcription of the pre-mRNA.  The RNA components of snRNPs interact with the intron and are involved in catalysis.  Two types of spliceosomes have been identified (major and minor) which contain different [[snRNP]]s.
* The '''major spliceosome''' splices introns containing GU at the 5' splice site and AG at the 3' splice site.  It is composed of the [[U1 spliceosomal RNA|U1]], [[U2 spliceosomal RNA|U2]], [[U4 spliceosomal RNA|U4]], [[U5 spliceosomal RNA|U5]], and [[U6 spliceosomal RNA|U6]] [[snRNP]]s and is active in the nucleus. In addition, a number of proteins including [[U2 small nuclear RNA auxiliary factor 1]] (U2AF35), [[U2AF2]] (U2AF65)<ref name=graveley2001>{{cite journal | vauthors = Graveley BR, Hertel KJ, Maniatis T | title = The role of U2AF35 and U2AF65 in enhancer-dependent splicing | journal = RNA | volume = 7 | issue = 6 | pages = 806–818 | date = June 2001 | pmid = 11421359 | pmc = 1370132 | doi = 10.1017/s1355838201010317 | doi-broken-date = 2024-11-08 | url = http://rnajournal.cshlp.org/content/7/6/806.abstract | access-date = 2014-12-17 | url-status = live | archive-url = https://web.archive.org/web/20181120053109/https://rnajournal.cshlp.org/content/7/6/806.abstract | archive-date = 2018-11-20 }}</ref> and [[SF1 (gene)|SF1]] are required for the assembly of the spliceosome.<ref name="Black"/><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 = 386–398 | date = May 2005 | pmid = 15956978 | doi = 10.1038/nrm1645 | s2cid = 14883495 }}</ref>  The spliceosome forms different complexes during the splicing process:<ref name=matera2014>{{cite journal | vauthors = Matera AG, Wang Z | title = A day in the life of the spliceosome | journal = Nature Reviews. Molecular Cell Biology | volume = 15 | issue = 2 | pages = 108–121 | date = February 2014 | pmid = 24452469 | pmc = 4060434 | doi = 10.1038/nrm3742 }}</ref>

:*Complex E
:**The U1 snRNP binds to the GU sequence at the 5' splice site of an intron;
:**[[SF1 (gene)|Splicing factor 1]] binds to the intron branch point sequence;
:**[[U2AF1]] binds at the 3' splice site of the intron;
:**[[U2AF2]] binds to the polypyrimidine tract;<ref name=guth2000>{{cite journal | vauthors = Guth S, Valcárcel J | title = Kinetic role for mammalian SF1/BBP in spliceosome assembly and function after polypyrimidine tract recognition by U2AF | journal = The Journal of Biological Chemistry | volume = 275 | issue = 48 | pages = 38059–38066 | date = December 2000 | pmid = 10954700 | doi = 10.1074/jbc.M001483200 | doi-access = free }}</ref>

:*Complex A (pre-spliceosome)
:**The U2 snRNP displaces SF1 and binds to the branch point sequence and ATP is hydrolyzed;

:*Complex B (pre-catalytic spliceosome)
:**The U5/U4/U6 snRNP trimer binds, and the U5 snRNP binds exons at the 5' site, with U6 binding to U2;

:*Complex B*
:**The U1 snRNP is released, U5 shifts from exon to intron, and the U6 binds at the 5' splice site;

:*Complex C (catalytic spliceosome)
:**U4 is released, U6/U2 catalyzes transesterification, making the 5'-end of the intron ligate to the A on intron and form a lariat, U5 binds exon at 3' splice site, and the 5' site is cleaved, resulting in the formation of the lariat;

:*Complex C* (post-spliceosomal complex)
:**U2/U5/U6 remain bound to the lariat, and the 3' site is cleaved and exons are ligated using ATP hydrolysis.  The spliced RNA is released, the lariat is released and degraded,<ref name=cheng2011>{{cite journal | vauthors = Cheng Z, Menees TM | title = RNA splicing and debranching viewed through analysis of RNA lariats | journal = Molecular Genetics and Genomics | volume = 286 | issue = 5–6 | pages = 395–410 | date = December 2011 | pmid = 22065066 | doi = 10.1007/s00438-011-0635-y | s2cid = 846297 }}</ref> and the snRNPs are recycled.

:This type of splicing is termed ''canonical splicing'' or termed the ''lariat pathway'', which accounts for more than 99% of splicing. By contrast, when the intronic flanking sequences do not follow the GU-AG rule, ''noncanonical splicing'' is said to occur (see "minor spliceosome" below).<ref>{{cite journal | vauthors = Ng B, Yang F, Huston DP, Yan Y, Yang Y, Xiong Z, Peterson LE, Wang H, Yang XF | display-authors = 6 | title = Increased noncanonical splicing of autoantigen transcripts provides the structural basis for expression of untolerized epitopes | journal = The Journal of Allergy and Clinical Immunology | volume = 114 | issue = 6 | pages = 1463–1470 | date = December 2004 | pmid = 15577853 | pmc = 3902068 | doi = 10.1016/j.jaci.2004.09.006 }}</ref>
* The '''[[minor spliceosome]]''' is very similar to the major spliceosome, but instead it splices out rare introns with different splice site sequences. While the minor and major spliceosomes contain the same U5 [[snRNP]], the minor spliceosome has different but functionally analogous snRNPs for U1, U2, U4, and U6, which are respectively called [[U11 spliceosomal RNA|U11]], [[U12 minor spliceosomal RNA|U12]], [[U4atac minor spliceosomal RNA|U4atac]], and [[U6atac minor spliceosomal RNA|U6atac]].<ref>{{cite journal | vauthors = Patel AA, Steitz JA | title = Splicing double: insights from the second spliceosome | journal = Nature Reviews. Molecular Cell Biology | volume = 4 | issue = 12 | pages = 960–970 | date = December 2003 | pmid = 14685174 | doi = 10.1038/nrm1259 | s2cid = 21816910 }}</ref>