SF3B4 explained

Splicing factor 3B subunit 4 is a protein that in humans is encoded by the SF3B4 gene.^{[1] [2]}

Function

This gene encodes one of four subunits of the splicing factor 3b. The protein encoded by this gene cross-links to a region in the pre-mRNA immediately upstream of the branchpoint sequence in pre-mRNA in the prespliceosomal complex A. It also may be involved in the assembly of the B, C and E spliceosomal complexes. In addition to RNA-binding activity, this protein interacts directly and highly specifically with subunit 2 of the splicing factor 3B. This protein contains two N-terminal RNA-recognition motifs (RRMs), consistent with the observation that it binds directly to pre-mRNA.

Disease associations

In 2012, Canadian researchers belonging to the FORGE (Finding of Rare disease GEnes) consortium identified new dominant mutations in SF3B4 as the cause of Nager syndrome, a rare type of mandibulofacial dysostosis with associated limb malformations.^[3]

Interactions

SF3B4 has been shown to interact with CDC5L,^[4] BMPR1A^[5] and SF3B2.^[6]

Further reading

• Maruyama K, Sugano S . Oligo-capping: a simple method to replace the cap structure of eukaryotic mRNAs with oligoribonucleotides . Gene . 138 . 1–2 . 171–4 . Jan 1994 . 8125298 . 10.1016/0378-1119(94)90802-8 .
• Suzuki Y, Yoshitomo-Nakagawa K, Maruyama K, Suyama A, Sugano S . Construction and characterization of a full length-enriched and a 5'-end-enriched cDNA library . Gene . 200 . 1–2 . 149–56 . Oct 1997 . 9373149 . 10.1016/S0378-1119(97)00411-3 .
• Neubauer G, King A, Rappsilber J, Calvio C, Watson M, Ajuh P, Sleeman J, Lamond A, Mann M . Mass spectrometry and EST-database searching allows characterization of the multi-protein spliceosome complex . Nature Genetics . 20 . 1 . 46–50 . Sep 1998 . 9731529 . 10.1038/1700 . 585778 .
• Das BK, Xia L, Palandjian L, Gozani O, Chyung Y, Reed R . Characterization of a protein complex containing spliceosomal proteins SAPs 49, 130, 145, and 155 . Molecular and Cellular Biology . 19 . 10 . 6796–802 . Oct 1999 . 10490618 . 84676 . 10.1128/mcb.19.10.6796.
• Das R, Zhou Z, Reed R . Functional association of U2 snRNP with the ATP-independent spliceosomal complex E . Molecular Cell . 5 . 5 . 779–87 . May 2000 . 10882114 . 10.1016/S1097-2765(00)80318-4 . free .
• Will CL, Schneider C, MacMillan AM, Katopodis NF, Neubauer G, Wilm M, Lührmann R, Query CC . A novel U2 and U11/U12 snRNP protein that associates with the pre-mRNA branch site . The EMBO Journal . 20 . 16 . 4536–46 . Aug 2001 . 11500380 . 125580 . 10.1093/emboj/20.16.4536 .
• Will CL, Urlaub H, Achsel T, Gentzel M, Wilm M, Lührmann R . Characterization of novel SF3b and 17S U2 snRNP proteins, including a human Prp5p homologue and an SF3b DEAD-box protein . The EMBO Journal . 21 . 18 . 4978–88 . Sep 2002 . 12234937 . 126279 . 10.1093/emboj/cdf480 .
• Golas MM, Sander B, Will CL, Lührmann R, Stark H . Molecular architecture of the multiprotein splicing factor SF3b . Science . 300 . 5621 . 980–4 . May 2003 . 12738865 . 10.1126/science.1084155 . 2003Sci...300..980G . 31046270 .
• Lehner B, Semple JI, Brown SE, Counsell D, Campbell RD, Sanderson CM . Analysis of a high-throughput yeast two-hybrid system and its use to predict the function of intracellular proteins encoded within the human MHC class III region . Genomics . 83 . 1 . 153–67 . Jan 2004 . 14667819 . 10.1016/S0888-7543(03)00235-0 .
• Will CL, Schneider C, Hossbach M, Urlaub H, Rauhut R, Elbashir S, Tuschl T, Lührmann R . The human 18S U11/U12 snRNP contains a set of novel proteins not found in the U2-dependent spliceosome . RNA . 10 . 6 . 929–41 . Jun 2004 . 15146077 . 1370585 . 10.1261/rna.7320604 .
• Nishanian TG, Waldman T . Interaction of the BMPR-IA tumor suppressor with a developmentally relevant splicing factor . Biochemical and Biophysical Research Communications . 323 . 1 . 91–7 . Oct 2004 . 15351706 . 10.1016/j.bbrc.2004.08.060 .
• Lin KT, Lu RM, Tarn WY . The WW domain-containing proteins interact with the early spliceosome and participate in pre-mRNA splicing in vivo . Molecular and Cellular Biology . 24 . 20 . 9176–85 . Oct 2004 . 15456888 . 517884 . 10.1128/MCB.24.20.9176-9185.2004 .
• Rush J, Moritz A, Lee KA, Guo A, Goss VL, Spek EJ, Zhang H, Zha XM, Polakiewicz RD, Comb MJ . Immunoaffinity profiling of tyrosine phosphorylation in cancer cells . Nature Biotechnology . 23 . 1 . 94–101 . Jan 2005 . 15592455 . 10.1038/nbt1046 . 7200157 .
• 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 . Towards a proteome-scale map of the human protein-protein interaction network . Nature . 437 . 7062 . 1173–8 . Oct 2005 . 16189514 . 10.1038/nature04209 . 2005Natur.437.1173R . 4427026 .
• Guo D, Han J, Adam BL, Colburn NH, Wang MH, Dong Z, Eizirik DL, She JX, Wang CY . Proteomic analysis of SUMO4 substrates in HEK293 cells under serum starvation-induced stress . Biochemical and Biophysical Research Communications . 337 . 4 . 1308–18 . Dec 2005 . 16236267 . 10.1016/j.bbrc.2005.09.191 .
• Terada Y, Yasuda Y . Human immunodeficiency virus type 1 Vpr induces G2 checkpoint activation by interacting with the splicing factor SAP145 . Molecular and Cellular Biology . 26 . 21 . 8149–58 . Nov 2006 . 16923959 . 1636759 . 10.1128/MCB.01170-06 .

Notes and References

1. Champion-Arnaud P, Reed R . The prespliceosome components SAP 49 and SAP 145 interact in a complex implicated in tethering U2 snRNP to the branch site . Genes & Development . 8 . 16 . 1974–83 . Aug 1994 . 7958871 . 10.1101/gad.8.16.1974 . free .
2. Web site: Entrez Gene: SF3B4 splicing factor 3b, subunit 4, 49kDa.
3. Bernier FP, Caluseriu O, Ng S, Schwartzentruber J, Buckingham KJ, Innes AM, Jabs EW, Innis JW, Schuette JL, Gorski JL, Byers PH, Andelfinger G, Siu V, Lauzon J, Fernandez BA, McMillin M, Scott RH, Racher H, Majewski J, Nickerson DA, Shendure J, Bamshad MJ, Parboosingh JS . Haploinsufficiency of SF3B4, a component of the pre-mRNA spliceosomal complex, causes Nager syndrome . American Journal of Human Genetics . 90 . 5 . 925–33 . May 2012 . 22541558 . 3376638 . 10.1016/j.ajhg.2012.04.004 .
4. Ajuh P, Kuster B, Panov K, Zomerdijk JC, Mann M, Lamond AI . Functional analysis of the human CDC5L complex and identification of its components by mass spectrometry . The EMBO Journal . 19 . 23 . 6569–81 . Dec 2000 . 11101529 . 305846 . 10.1093/emboj/19.23.6569 .
5. Nishanian TG, Waldman T . Interaction of the BMPR-IA tumor suppressor with a developmentally relevant splicing factor . Biochemical and Biophysical Research Communications . 323 . 1 . 91–7 . Oct 2004 . 15351706 . 10.1016/j.bbrc.2004.08.060 .
6. Huda Zoghbi . 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 . Towards a proteome-scale map of the human protein-protein interaction network . Nature . 437 . 7062 . 1173–8 . Oct 2005 . 16189514 . 10.1038/nature04209 . 2005Natur.437.1173R . 4427026 .