SnRNP70 explained

snRNP70 also known as U1 small nuclear ribonucleoprotein 70 kDa is a protein^[1] that in humans is encoded by the SNRNP70 gene.^{[2] [3]} snRNP70 is a small nuclear ribonucleoprotein that associates with U1 spliceosomal RNA, forming the U1snRNP a core component of the spliceosome. The U1-70K protein and other components of the spliceosome complex form detergent-insoluble aggregates in both sporadic and familial human cases of Alzheimer's disease.^{[4] [5]} U1-70K co-localizes with Tau in neurofibrillary tangles in Alzheimer's disease.

Interactions

snRNP70 has been shown to interact with ASF/SF2,^{[6] [7]} SRPK1,^{[8] [9]} and ZRANB2.^[10]

Role in autoimmunity

Antibodies towards snRNP70 are associated with mixed connective tissue disease.^[11]

Further reading

• Wilk HE, Schaefer KP, Agris PF, Boak AM, Kovacs SA . U1 SnRNP association with HnRNP involves an initial non-specific splice-site independent interaction of U1 SnRNP protein with HnRNA . Molecular and Cellular Biochemistry . 106 . 1 . 55–66 . July 1991 . 1833625 . 10.1007/BF00231189 . 22696966 .
• Query CC, Bentley RC, Keene JD . A common RNA recognition motif identified within a defined U1 RNA binding domain of the 70K U1 snRNP protein . Cell . 57 . 1 . 89–101 . April 1989 . 2467746 . 10.1016/0092-8674(89)90175-X . 22127152 .
• Du Clos TW . C-reactive protein reacts with the U1 small nuclear ribonucleoprotein . Journal of Immunology . 143 . 8 . 2553–9 . October 1989 . 10.4049/jimmunol.143.8.2553 . 2477447 . 84070596 . free .
• Theissen H, Etzerodt M, Reuter R, Schneider C, Lottspeich F, Argos P, Lührmann R, Philipson L . Cloning of the human cDNA for the U1 RNA-associated 70K protein . The EMBO Journal . 5 . 12 . 3209–17 . December 1986 . 3028775 . 1167314 . 10.1002/j.1460-2075.1986.tb04631.x.
• Romac JM, Graff DH, Keene JD . The U1 small nuclear ribonucleoprotein (snRNP) 70K protein is transported independently of U1 snRNP particles via a nuclear localization signal in the RNA-binding domain . Molecular and Cellular Biology . 14 . 7 . 4662–70 . July 1994 . 7516470 . 358839 . 10.1128/MCB.14.7.4662.
• Wu JY, Maniatis T . Specific interactions between proteins implicated in splice site selection and regulated alternative splicing . Cell . 75 . 6 . 1061–70 . December 1993 . 8261509 . 10.1016/0092-8674(93)90316-I . 22951690 .
• Woppmann A, Will CL, Kornstädt U, Zuo P, Manley JL, Lührmann R . Identification of an snRNP-associated kinase activity that phosphorylates arginine/serine rich domains typical of splicing factors . Nucleic Acids Research . 21 . 12 . 2815–22 . June 1993 . 8332490 . 309659 . 10.1093/nar/21.12.2815 .
• Northemann W, Berg H, Stahnke G, Walter M, Hunt N, Fenning S . Identification of an inhibitory element within the human 68-kDa (U1) ribonucleoprotein antigen . Protein Expression and Purification . 6 . 6 . 748–56 . December 1995 . 8746626 . 10.1006/prep.1995.0005 .
• Zhang WJ, Wu JY . Functional properties of p54, a novel SR protein active in constitutive and alternative splicing . Molecular and Cellular Biology . 16 . 10 . 5400–8 . October 1996 . 8816452 . 231539 . 10.1128/MCB.16.10.5400.
• Bonaldo MF, Lennon G, Soares MB . Normalization and subtraction: two approaches to facilitate gene discovery . Genome Research . 6 . 9 . 791–806 . September 1996 . 8889548 . 10.1101/gr.6.9.791 . free .
• Hong W, Bennett M, Xiao Y, Feld Kramer R, Wang C, Reed R . Association of U2 snRNP with the spliceosomal complex E . Nucleic Acids Research . 25 . 2 . 354–61 . January 1997 . 9016565 . 146436 . 10.1093/nar/25.2.354 .
• Klein Gunnewiek JM, van Aarssen Y, van der Kemp A, Nelissen R, Pruijn GJ, van Venrooij WJ . Nuclear accumulation of the U1 snRNP-specific protein C is due to diffusion and retention in the nucleus . Experimental Cell Research . 235 . 1 . 265–73 . August 1997 . 9281376 . 10.1006/excr.1997.3663 .
• Zhang WJ, Wu JY . Sip1, a novel RS domain-containing protein essential for pre-mRNA splicing . Molecular and Cellular Biology . 18 . 2 . 676–84 . February 1998 . 9447963 . 108778 . 10.1128/MCB.18.2.676.
• Blencowe BJ, Issner R, Nickerson JA, Sharp PA . A coactivator of pre-mRNA splicing . Genes & Development . 12 . 7 . 996–1009 . April 1998 . 9531537 . 316672 . 10.1101/gad.12.7.996 .
• Cao W, Garcia-Blanco MA . A serine/arginine-rich domain in the human U1 70k protein is necessary and sufficient for ASF/SF2 binding . The Journal of Biological Chemistry . 273 . 32 . 20629–35 . August 1998 . 9685421 . 10.1074/jbc.273.32.20629 . free .
• 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 . September 1998 . 9731529 . 10.1038/1700 . 585778 .
• Xiao SH, Manley JL . Phosphorylation-dephosphorylation differentially affects activities of splicing factor ASF/SF2 . The EMBO Journal . 17 . 21 . 6359–67 . November 1998 . 9799243 . 1170960 . 10.1093/emboj/17.21.6359 .
• Dumortier H, Klein Gunnewiek J, Roussel JP, van Aarssen Y, Briand JP, van Venrooij WJ, Muller S . At least three linear regions but not the zinc-finger domain of U1C protein are exposed at the surface of the protein in solution and on the human spliceosomal U1 snRNP particle . Nucleic Acids Research . 26 . 23 . 5486–91 . December 1998 . 9826776 . 147990 . 10.1093/nar/26.23.5486 .

Notes and References

1. Spritz RA, Strunk K, Surowy CS, Hoch SO, Barton DE, Francke U . The human U1-70K snRNP protein: cDNA cloning, chromosomal localization, expression, alternative splicing and RNA-binding . Nucleic Acids Research . 15 . 24 . 10373–91 . December 1987 . 2447561 . 339950 . 10.1093/nar/15.24.10373 .
2. Web site: Entrez Gene: SNRP70 small nuclear ribonucleoprotein 70kDa polypeptide (RNP antigen).
3. Spritz RA, Strunk K, Surowy CS, Mohrenweiser HW . Human U1-70K ribonucleoprotein antigen gene: organization, nucleotide sequence, and mapping to locus 19q13.3 . Genomics . 8 . 2 . 371–9 . October 1990 . 2147422 . 10.1016/0888-7543(90)90295-6 .
4. Diner I, Hales CM, Bishof I, Rabenold L, Duong DM, Yi H, Laur O, Gearing M, Troncoso J, Thambisetty M, Lah JJ, Levey AI, Seyfried NT . Aggregation properties of the small nuclear ribonucleoprotein U1-70K in Alzheimer disease . The Journal of Biological Chemistry . 289 . 51 . 35296–313 . December 2014 . 25355317 . 4271217 . 10.1074/jbc.M114.562959 . free .
5. Hales CM, Seyfried NT, Dammer EB, Duong D, Yi H, Gearing M, Troncoso JC, Mufson EJ, Thambisetty M, Levey AI, Lah JJ . U1 small nuclear ribonucleoproteins (snRNPs) aggregate in Alzheimer's disease due to autosomal dominant genetic mutations and trisomy 21 . Molecular Neurodegeneration . 9 . 15 . April 2014 . 24773620 . 4022210 . 10.1186/1750-1326-9-15 . free .
6. Xiao SH, Manley JL . Phosphorylation-dephosphorylation differentially affects activities of splicing factor ASF/SF2 . The EMBO Journal . 17 . 21 . 6359–67 . November 1998 . 9799243 . 1170960 . 10.1093/emboj/17.21.6359 .
7. Cao W, Garcia-Blanco MA . A serine/arginine-rich domain in the human U1 70k protein is necessary and sufficient for ASF/SF2 binding . The Journal of Biological Chemistry . 273 . 32 . 20629–35 . August 1998 . 9685421 . 10.1074/jbc.273.32.20629 . free .
8. Wang HY, Lin W, Dyck JA, Yeakley JM, Songyang Z, Cantley LC, Fu XD . SRPK2: a differentially expressed SR protein-specific kinase involved in mediating the interaction and localization of pre-mRNA splicing factors in mammalian cells . The Journal of Cell Biology . 140 . 4 . 737–50 . February 1998 . 9472028 . 2141757 . 10.1083/jcb.140.4.737 .
9. Kamachi M, Le TM, Kim SJ, Geiger ME, Anderson P, Utz PJ . Human autoimmune sera as molecular probes for the identification of an autoantigen kinase signaling pathway . The Journal of Experimental Medicine . 196 . 9 . 1213–25 . November 2002 . 12417631 . 2194102 . 10.1084/jem.20021167 .
10. Adams DJ, van der Weyden L, Mayeda A, Stamm S, Morris BJ, Rasko JE . ZNF265--a novel spliceosomal protein able to induce alternative splicing . The Journal of Cell Biology . 154 . 1 . 25–32 . July 2001 . 11448987 . 2196870 . 10.1083/jcb.200010059 .
11. Sato T, Fujii T, Yokoyama T, Fujita Y, Imura Y, Yukawa N, Kawabata D, Nojima T, Ohmura K, Usui T, Mimori T . Anti-U1 RNP antibodies in cerebrospinal fluid are associated with central neuropsychiatric manifestations in systemic lupus erythematosus and mixed connective tissue disease . Arthritis and Rheumatism . 62 . 12 . 3730–40 . December 2010 . 20722023 . 10.1002/art.27700 . 2433/142082 . free .