Fission Yeast Prp4p Kinase Regulates Pre-mRNA Splicing by Phosphorylating a Non-SR-splicing Factor

Overview

Journal EMBO Rep

Specialty Molecular Biology

Date 2001 Mar 17

PMID 11252721

Citations 23

Authors

W Schwelnus

K Richert

F Opitz

T Gross

Y Habara

T Tani

N F Kaufer

Affiliations

Soon will be listed here.

Abstract

We provide evidence that Prp4p kinase activity is required for pre-mRNA splicing in vivo and show that loss of activity impairs G1-S and G2-M progression in the cell cycle. Prp4p interacts genetically with the non-SR (serine/arginine) splicing factors Prp1p and Prp5p. Bacterially produced Prp1p is phosphorylated by Prp4p in vitro. Prp4p and Prp1p also interact in the yeast two-hybrid system. In vivo labelling studies using a strain with a mutant allele of the prp4 gene in the genetic background indicate a change in phosphorylation of the Prp1p protein. These results are consistent with the notion that Prp4p kinase is involved in the control of the formation of active spliceosomes, targeting non-SR splicing factors.

Citing Articles

Tinker, Tailor, Tumour Suppressor: The Many Functions of PRP4K.

Habib E, Mathavarajah S, Dellaire G Front Genet. 2022; 13:839963.

PMID: 35281802 PMC: 8912934. DOI: 10.3389/fgene.2022.839963.

PRP4 Promotes Skin Cancer by Inhibiting Production of Melanin, Blocking Influx of Extracellular Calcium, and Remodeling Cell Actin Cytoskeleton.

Ahmed M, Islam S, Lee Y Int J Mol Sci. 2021; 22(13).

PMID: 34209674 PMC: 8268783. DOI: 10.3390/ijms22136992.

Interplay Between CMGC Kinases Targeting SR Proteins and Viral Replication: Splicing and Beyond.

Pastor F, Shkreta L, Chabot B, Durantel D, Salvetti A Front Microbiol. 2021; 12:658721.

PMID: 33854493 PMC: 8040976. DOI: 10.3389/fmicb.2021.658721.

PRPF overexpression induces drug resistance through actin cytoskeleton rearrangement and epithelial-mesenchymal transition.

Islam S, Shehzad A, Sonn J, Lee Y Oncotarget. 2017; 8(34):56659-56671.

PMID: 28915620 PMC: 5593591. DOI: 10.18632/oncotarget.17855.

The Fission Yeast Pre-mRNA-processing Factor 18 (prp18+) Has Intron-specific Splicing Functions with Links to G1-S Cell Cycle Progression.

Vijaykrishna N, Melangath G, Kumar R, Khandelia P, Bawa P, Varadarajan R J Biol Chem. 2016; 291(53):27387-27402.

PMID: 27875300 PMC: 5207164. DOI: 10.1074/jbc.M116.751289.

References

Lundgren K, Allan S, Urushiyama S, Tani T, Ohshima Y, Frendewey D . A connection between pre-mRNA splicing and the cell cycle in fission yeast: cdc28+ is allelic with prp8+ and encodes an RNA-dependent ATPase/helicase. Mol Biol Cell. 1996; 7(7):1083-94. PMC: 275960. DOI: 10.1091/mbc.7.7.1083. View

Lutzelberger M, Gross T, Kaufer N . Srp2, an SR protein family member of fission yeast: in vivo characterization of its modular domains. Nucleic Acids Res. 1999; 27(13):2618-26. PMC: 148469. DOI: 10.1093/nar/27.13.2618. View

Gross T, Lutzelberger M, Weigmann H, Klingenhoff A, Shenoy S, Kaufer N . Functional analysis of the fission yeast Prp4 protein kinase involved in pre-mRNA splicing and isolation of a putative mammalian homologue. Nucleic Acids Res. 1997; 25(5):1028-35. PMC: 146536. DOI: 10.1093/nar/25.5.1028. View

Will C, Luhrmann R . Protein functions in pre-mRNA splicing. Curr Opin Cell Biol. 1997; 9(3):320-8. DOI: 10.1016/s0955-0674(97)80003-8. View

Urushiyama S, Tani T, Ohshima Y . The prp1+ gene required for pre-mRNA splicing in Schizosaccharomyces pombe encodes a protein that contains TPR motifs and is similar to Prp6p of budding yeast. Genetics. 1997; 147(1):101-15. PMC: 1208094. DOI: 10.1093/genetics/147.1.101. View

Gross T, Richert K, Mierke C, Lutzelberger M, Kaufer N . Identification and characterization of srp1, a gene of fission yeast encoding a RNA binding domain and a RS domain typical of SR splicing factors. Nucleic Acids Res. 1998; 26(2):505-11. PMC: 147300. DOI: 10.1093/nar/26.2.505. View

Tang Z, Yanagida M, Lin R . Fission yeast mitotic regulator Dsk1 is an SR protein-specific kinase. J Biol Chem. 1998; 273(10):5963-9. DOI: 10.1074/jbc.273.10.5963. View

Schmidt H, Richert K, Drakas R, Kaufer N . spp42, identified as a classical suppressor of prp4-73, which encodes a kinase involved in pre-mRNA splicing in fission yeast, is a homologue of the splicing factor Prp8p. Genetics. 1999; 153(3):1183-91. PMC: 1460826. DOI: 10.1093/genetics/153.3.1183. View

Tang Z, Kuo T, Shen J, Lin R . Biochemical and genetic conservation of fission yeast Dsk1 and human SR protein-specific kinase 1. Mol Cell Biol. 2000; 20(3):816-24. PMC: 85198. DOI: 10.1128/MCB.20.3.816-824.2000. View

10.

Makarov E, Makarova O, Achsel T, Luhrmann R . The human homologue of the yeast splicing factor prp6p contains multiple TPR elements and is stably associated with the U5 snRNP via protein-protein interactions. J Mol Biol. 2000; 298(4):567-75. DOI: 10.1006/jmbi.2000.3685. View

11.

Beales M, Flay N, McKinney R, Habara Y, Ohshima Y, Tani T . Mutations in the large subunit of U2AF disrupt pre-mRNA splicing, cell cycle progression and nuclear structure. Yeast. 2000; 16(11):1001-13. DOI: 10.1002/1097-0061(200008)16:11<1001::AID-YEA605>3.0.CO;2-6. View

12.

Kaufer N, Potashkin J . Analysis of the splicing machinery in fission yeast: a comparison with budding yeast and mammals. Nucleic Acids Res. 2000; 28(16):3003-10. PMC: 108416. DOI: 10.1093/nar/28.16.3003. View

13.

Potashkin J, Li R, Frendewey D . Pre-mRNA splicing mutants of Schizosaccharomyces pombe. EMBO J. 1989; 8(2):551-9. PMC: 400840. DOI: 10.1002/j.1460-2075.1989.tb03409.x. View

14.

Moreno S, Klar A, Nurse P . Molecular genetic analysis of fission yeast Schizosaccharomyces pombe. Methods Enzymol. 1991; 194:795-823. DOI: 10.1016/0076-6879(91)94059-l. View

15.

Rosenberg G, Alahari S, Kaufer N . prp4 from Schizosaccharomyces pombe, a mutant deficient in pre-mRNA splicing isolated using genes containing artificial introns. Mol Gen Genet. 1991; 226(1-2):305-9. DOI: 10.1007/BF00273617. View

16.

Galisson F, Legrain P . The biochemical defects of prp4-1 and prp6-1 yeast splicing mutants reveal that the PRP6 protein is required for the accumulation of the [U4/U6.U5] tri-snRNP. Nucleic Acids Res. 1993; 21(7):1555-62. PMC: 309362. DOI: 10.1093/nar/21.7.1555. View

17.

Tazi J, Kornstadt U, Rossi F, Jeanteur P, Cathala G, Brunel C . Thiophosphorylation of U1-70K protein inhibits pre-mRNA splicing. Nature. 1993; 363(6426):283-6. DOI: 10.1038/363283a0. View

18.

Alahari S, Schmidt H, Kaufer N . The fission yeast prp4+ gene involved in pre-mRNA splicing codes for a predicted serine/threonine kinase and is essential for growth. Nucleic Acids Res. 1993; 21(17):4079-83. PMC: 310008. DOI: 10.1093/nar/21.17.4079. View

19.

Gui J, Lane W, Fu X . A serine kinase regulates intracellular localization of splicing factors in the cell cycle. Nature. 1994; 369(6482):678-82. DOI: 10.1038/369678a0. View

20.

Mermoud J, Cohen P, Lamond A . Regulation of mammalian spliceosome assembly by a protein phosphorylation mechanism. EMBO J. 1994; 13(23):5679-88. PMC: 395533. DOI: 10.1002/j.1460-2075.1994.tb06906.x. View