U2AF2

{{Short description|Protein-coding gene in the species Homo sapiens}}

Splicing factor U2AF 65 kDa subunit is a protein that in humans is encoded by the U2AF2 gene.{{cite journal | vauthors = Zamore PD, Patton JG, Green MR | title = Cloning and domain structure of the mammalian splicing factor U2AF | journal = Nature | volume = 355 | issue = 6361 | pages = 609–614 | date = February 1992 | pmid = 1538748 | doi = 10.1038/355609a0 | s2cid = 4332390 | bibcode = 1992Natur.355..609Z }}

Function

In eukaryotes, the introns in the transcribed pre-mRNA first have to be removed by spliceosome in order to form a mature mRNA. A spliceosome is assembled from small nuclear ribonucleoproteins(snRNP) and small nuclear RNAs(snRNA). And the splicing factor can be divided into snRNP and non snRNP proteins.U2 auxiliary factor (U2AF), composed of a large and a small subunit, is a non-snRNP protein required for the binding of U2 snRNP to the pre-mRNA branch site. This gene encodes the U2AF large subunit, which contains a sequence-specific RNA-binding region with 3 RNA recognition motifs and an Arg/Ser-rich domain necessary for splicing. The large subunit binds to the polypyrimidine tract of introns early during spliceosome assembly. Multiple alternatively spliced transcript variants have been detected for this gene, but the full-length natures of only two have been determined to date.{{cite web | title = Entrez Gene: U2AF2 U2 small nuclear RNA auxiliary factor 2| url = https://www.ncbi.nlm.nih.gov/sites/entrez?Db=gene&Cmd=ShowDetailView&TermToSearch=11338}}

In humans and other tetrapods, it has been shown that without U2AF2, the splicing process is inhibited. However, in zebrafish and other teleosts the RNA splicing process can still occur on certain genes in the absence of U2AF2. This may be because 10% of genes have alternating TG and AC base pairs at the 3' splice site (3'ss) and 5' splice site (5'ss) respectively on each intron, which alters the secondary structure of the RNA and influences splicing.{{cite journal | vauthors = Lin CL, Taggart AJ, Lim KH, Cygan KJ, Ferraris L, Creton R, Huang YT, Fairbrother WG | display-authors = 6 | title = RNA structure replaces the need for U2AF2 in splicing | journal = Genome Research | volume = 26 | issue = 1 | pages = 12–23 | date = January 2016 | pmid = 26566657 | pmc = 4691745 | doi = 10.1101/gr.181008.114 }}

The splicing factor U2AF65 can specifically recognize the polypyrimidine tract (Py tract), that’s because U2AF65 consists of 3 RNA binding domains (RRMs), all of them have a high binding affinity to the Py tract on its adjacent 3’ splice site. The RRM1 and RRM2 are sufficient for specific RNA/protein binding, while RRM3 is responsible for protein/protein interactions. For example, the C-Terminal RRM3 contribute to establish protein–protein contacts with splicing factors like UAP56, SAP155, and mBBP/SF1.{{cite journal | vauthors = Selenko P, Gregorovic G, Sprangers R, Stier G, Rhani Z, Krämer A, Sattler M | title = Structural basis for the molecular recognition between human splicing factors U2AF65 and SF1/mBBP | journal = Molecular Cell | volume = 11 | issue = 4 | pages = 965–976 | date = April 2003 | pmid = 12718882 | doi = 10.1016/s1097-2765(03)00115-1 | doi-access = free }}

Interactions

U2AF2 has been shown to interact with:

PUF60,{{cite journal | vauthors = Rual JF, Venkatesan K, Hao T, Hirozane-Kishikawa T, Dricot A, Li N, Berriz GF, Gibbons FD, Dreze M, Ayivi-Guedehoussou N, Klitgord N, Simon C, Boxem M, Milstein S, Rosenberg J, Goldberg DS, Zhang LV, Wong SL, Franklin G, Li S, Albala JS, Lim J, Fraughton C, Llamosas E, Cevik S, Bex C, Lamesch P, Sikorski RS, Vandenhaute J, Zoghbi HY, Smolyar A, Bosak S, Sequerra R, Doucette-Stamm L, Cusick ME, Hill DE, Roth FP, Vidal M | display-authors = 6 | title = Towards a proteome-scale map of the human protein-protein interaction network | journal = Nature | volume = 437 | issue = 7062 | pages = 1173–1178 | date = October 2005 | pmid = 16189514 | doi = 10.1038/nature04209 | s2cid = 4427026 | bibcode = 2005Natur.437.1173R }}{{cite journal | vauthors = Ewing RM, Chu P, Elisma F, Li H, Taylor P, Climie S, McBroom-Cerajewski L, Robinson MD, O'Connor L, Li M, Taylor R, Dharsee M, Ho Y, Heilbut A, Moore L, Zhang S, Ornatsky O, Bukhman YV, Ethier M, Sheng Y, Vasilescu J, Abu-Farha M, Lambert JP, Duewel HS, Stewart II, Kuehl B, Hogue K, Colwill K, Gladwish K, Muskat B, Kinach R, Adams SL, Moran MF, Morin GB, Topaloglou T, Figeys D | display-authors = 6 | title = Large-scale mapping of human protein-protein interactions by mass spectrometry | journal = Molecular Systems Biology | volume = 3 | pages = 89 | year = 2007 | pmid = 17353931 | pmc = 1847948 | doi = 10.1038/msb4100134 }}
SF1,{{cite journal | vauthors = Berglund JA, Abovich N, Rosbash M | title = A cooperative interaction between U2AF65 and mBBP/SF1 facilitates branchpoint region recognition | journal = Genes & Development | volume = 12 | issue = 6 | pages = 858–867 | date = March 1998 | pmid = 9512519 | pmc = 316625 | doi = 10.1101/gad.12.6.858 }}{{cite journal | vauthors = Abovich N, Rosbash M | title = Cross-intron bridging interactions in the yeast commitment complex are conserved in mammals | journal = Cell | volume = 89 | issue = 3 | pages = 403–412 | date = May 1997 | pmid = 9150140 | doi = 10.1016/s0092-8674(00)80221-4 | s2cid = 18466775 | doi-access = free }}
SFRS11,{{cite journal | vauthors = Zhang WJ, Wu JY | title = Functional properties of p54, a novel SR protein active in constitutive and alternative splicing | journal = Molecular and Cellular Biology | volume = 16 | issue = 10 | pages = 5400–5408 | date = October 1996 | pmid = 8816452 | pmc = 231539 | doi = 10.1128/MCB.16.10.5400 }}
SFRS2IP,{{cite journal | vauthors = Zhang WJ, Wu JY | title = Sip1, a novel RS domain-containing protein essential for pre-mRNA splicing | journal = Molecular and Cellular Biology | volume = 18 | issue = 2 | pages = 676–684 | date = February 1998 | pmid = 9447963 | pmc = 108778 | doi = 10.1128/MCB.18.2.676 }}
SRPK2,{{cite journal | vauthors = Wang HY, Lin W, Dyck JA, Yeakley JM, Songyang Z, Cantley LC, Fu XD | title = SRPK2: a differentially expressed SR protein-specific kinase involved in mediating the interaction and localization of pre-mRNA splicing factors in mammalian cells | journal = The Journal of Cell Biology | volume = 140 | issue = 4 | pages = 737–750 | date = February 1998 | pmid = 9472028 | pmc = 2141757 | doi = 10.1083/jcb.140.4.737 }}
U2 small nuclear RNA auxiliary factor 1{{cite journal | vauthors = Zhang M, Zamore PD, Carmo-Fonseca M, Lamond AI, Green MR | title = Cloning and intracellular localization of the U2 small nuclear ribonucleoprotein auxiliary factor small subunit | journal = Proceedings of the National Academy of Sciences of the United States of America | volume = 89 | issue = 18 | pages = 8769–8773 | date = September 1992 | pmid = 1388271 | pmc = 50002 | doi = 10.1073/pnas.89.18.8769 | doi-access = free | bibcode = 1992PNAS...89.8769Z }} and
WT1.{{cite journal | vauthors = Davies RC, Calvio C, Bratt E, Larsson SH, Lamond AI, Hastie ND | title = WT1 interacts with the splicing factor U2AF65 in an isoform-dependent manner and can be incorporated into spliceosomes | journal = Genes & Development | volume = 12 | issue = 20 | pages = 3217–3225 | date = October 1998 | pmid = 9784496 | pmc = 317218 | doi = 10.1101/gad.12.20.3217 }}

U2AF2

Function

Interactions

References

Further reading