Editing Spliceosome (section)

==Composition==
Each spliceosome is composed of five [[small nuclear RNA]]s (snRNA) and a range of associated protein factors. When these small RNAs are combined with the protein factors, they make RNA-protein complexes called [[snRNP]]s (<u>s</u>mall <u>n</u>uclear <u>r</u>ibo<u>n</u>ucleo<u>p</u>roteins, pronounced "snurps").
The snRNAs that make up the major spliceosome are named [[U1 snRNA|U1]], [[U2 snRNA|U2]], [[U4 snRNA|U4]], [[U5 snRNA|U5]], and [[U6 snRNA|U6]], so-called because they are rich in [[uridine]], and participate in several RNA-RNA and RNA-protein interactions.<ref name="Spliceosome_review_2011"/>

The assembly of the spliceosome occurs on each [[Primary transcript|pre-mRNA]] (also known as heterogeneous nuclear RNA, hn-RNA) at each exon:intron junction. The pre-mRNA introns contains specific sequence elements that are recognized and utilized during spliceosome assembly.  These include the 5' end splice site, the branch point sequence, the polypyrimidine tract, and the 3' end splice site.  The spliceosome catalyzes the removal of introns, and the ligation of the flanking exons.{{cn|date=July 2024}}

Introns typically have a GU nucleotide sequence at the 5' end splice site, and an AG at the 3' end splice site.  The 3' splice site can be further defined by a variable length of polypyrimidines, called the [[polypyrimidine tract]] (PPT), which serves the dual function of recruiting factors to the 3' splice site and possibly recruiting factors to the [[branch point sequence]] (BPS).  The BPS contains the conserved [[adenosine]] required for the first step of splicing.{{cn|date=July 2024}}

Many proteins exhibit a zinc-binding motif, which underscores the importance of zinc in the splicing mechanism.<ref>{{cite journal | vauthors = Agafonov DE, Deckert J, Wolf E, Odenwälder P, Bessonov S, Will CL, Urlaub H, Lührmann R | title = Semiquantitative proteomic analysis of the human spliceosome via a novel two-dimensional gel electrophoresis method | journal = Molecular and Cellular Biology | volume = 31 | issue = 13 | pages = 2667–82 | date = July 2011 | pmid = 21536652 | pmc = 3133382 | doi = 10.1128/mcb.05266-11 }}</ref><ref>{{cite journal | vauthors = Kuhn AN, van Santen MA, Schwienhorst A, Urlaub H, Lührmann R | title = Stalling of spliceosome assembly at distinct stages by small-molecule inhibitors of protein acetylation and deacetylation | journal = RNA | volume = 15 | issue = 1 | pages = 153–75 | date = January 2009 | pmid = 19029308 | pmc = 2612777 | doi = 10.1261/rna.1332609 }}</ref><ref>{{cite journal | vauthors = Patil V, Canzoneri JC, Samatov TR, Lührmann R, Oyelere AK | title = Molecular architecture of zinc chelating small molecules that inhibit spliceosome assembly at an early stage | journal = RNA | volume = 18 | issue = 9 | pages = 1605–11 | date = September 2012 | pmid = 22832025 | pmc = 3425776 | doi = 10.1261/rna.034819.112 }}</ref> The first molecular-resolution reconstruction of U4/U6.U5 triple small nuclear ribonucleoprotein (tri-snRNP) complex was reported in 2016.<ref>{{cite journal | vauthors = Cate JH | title = STRUCTURE. A Big Bang in spliceosome structural biology | journal = Science | volume = 351 | issue = 6280 | pages = 1390–2 | date = March 2016 | pmid = 27013712 | doi = 10.1126/science.aaf4465 | s2cid = 206648185 }}</ref>

[[Image:Yeast tri-snRNP.jpg|thumb|600px|center|Figure 1. Above are [[electron microscopy]]<ref name="pmid18953335">{{cite journal | vauthors = Häcker I, Sander B, Golas MM, Wolf E, Karagöz E, Kastner B, Stark H, Fabrizio P, Lührmann R | title = Localization of Prp8, Brr2, Snu114 and U4/U6 proteins in the yeast tri-snRNP by electron microscopy | journal = Nature Structural & Molecular Biology | volume = 15 | issue = 11 | pages = 1206–12 | date = November 2008 | pmid = 18953335 | doi = 10.1038/nsmb.1506 | s2cid = 22982227 }}</ref> fields of negatively stained yeast (''Saccharomyces cerevisiae'') tri-snRNPs. Below left is a schematic illustration of the interaction of tri-snRNP proteins with the U4/U6 snRNA duplex. Below right is a cartoon model of the yeast tri-snRNP with shaded areas corresponding to U5 (gray), U4/U6 (orange) and the linker region (yellow).]]

Cryo-EM has been applied extensively by Shi et al. to elucidate the near-/atomic structure of spliceosome in both yeast<ref>{{cite journal | vauthors = Yan C, Hang J, Wan R, Huang M, Wong CC, Shi Y | title = Structure of a yeast spliceosome at 3.6-angstrom resolution | journal = Science | volume = 349 | issue = 6253 | pages = 1182–91 | date = September 2015 | pmid = 26292707 | doi = 10.1126/science.aac7629 | bibcode = 2015Sci...349.1182Y | s2cid = 22194712 }}</ref> and humans.<ref>{{cite journal | vauthors = Zhang X, Yan C, Hang J, Finci LI, Lei J, Shi Y | title = An Atomic Structure of the Human Spliceosome | journal = Cell | volume = 169 | issue = 5 | pages = 918–929.e14 | date = May 2017 | pmid = 28502770 | doi = 10.1016/j.cell.2017.04.033 | doi-access = free }}</ref> The molecular framework of spliceosome at near-atomic-resolution demonstrates Spp42 component of U5 snRNP forms a central scaffold and anchors the catalytic center in yeast. The atomic structure of the human spliceosome illustrates the step II component Slu7 adopts an extended structure, poised for selection of the 3'-splice site. All five metals (assigned as Mg2+) in the yeast complex are preserved in the human complex.{{cn|date=July 2024}}