Abstract
In the preceding study we found that Sm snRNPs and SerArg (SR) family proteins co-immunoprecipitate with Pol II molecules containing a hyperphosphorylated CTD (Kim et al., 1997). The association between Pol IIo and splicing factors is maintained in the absence of pre-mRNA, and the polymerase need not be transcriptionally engaged (Kim et al., 1997). The latter findings led us to hypothesize that a phosphorylated form of the CTD interacts with pre-mRNA splicing components in vivo. To test this idea, a nested set of CTD-derived proteins was assayed for the ability to alter the nuclear distribution of splicing factors, and to interfere with splicing in vivo. Proteins containing heptapeptides 1-52 (CTD52), 1-32 (CTD32), 1-26 (CTD26), 1-13 (CTD13), 1-6 (CTD6), 1-3 (CTD3), or 1 (CTD1) were expressed in mammalian cells. The CTD-derived proteins become phosphorylated in vivo, and accumulate in the nucleus even though they lack a conventional nuclear localization signal. CTD52 induces a selective reorganization of splicing factors from discrete nuclear domains to the diffuse nucleoplasm, and significantly, it blocks the accumulation of spliced, but not unspliced, human β-globin transcripts. The extent of splicing factor disruption, and the degree of inhibition of splicing, are proportional to the number of heptapeptides added to the protein. The above results indicate a functional interaction between Pol II's CTD and pre-mRNA splicing.
References
38
Referenced
107
10.1073/pnas.90.5.1947
/ Proc Natl Acad Sci USA / Immunocytochemical analysis of the coiled body in the cell cycle and during cell proliferation by Andrade (1993)10.1083/jcb.112.5.785
/ J Cell Biol / Identification of a novel nuclear domain by Ascoli (1991)10.1016/0092-8674(94)90182-1
/ Cell / Splicing of Balbiani Ring 1 gene premRNA occurs simultaneously with transcription by Barén (1994)10.1101/gad.2.6.754
/ Genes Dev / Splice site selection, rate of splicing, and alternative splicing on nascent transcripts by Beyer (1988){'key': '2023072206374530000_B5', 'first-page': '131', 'article-title': 'Visualization of RNA transcription and processing', 'volume': '2', 'author': 'Beyer', 'year': '1991', 'journal-title': 'Semin Cell Biol'}
/ Semin Cell Biol / Visualization of RNA transcription and processing by Beyer (1991)10.1083/jcb.127.3.593
/ J Cell Biol / Association of nuclear matrix antigens with exon-containing splicing complexes by Blencowe (1994){'key': '2023072206374530000_B7', 'first-page': '852', 'article-title': 'New proteins related to the SerArg family of splicing factors', 'volume': '1', 'author': 'Blencowe', 'year': '1995', 'journal-title': 'RNA'}
/ RNA / New proteins related to the SerArg family of splicing factors by Blencowe (1995)10.1073/pnas.93.16.8253
/ Proc Natl Acad Sci USA / A hyperphosphorylated form of the largest subunit of RNA polymerase II is associated with splicing complexes by Blencowe (1996)10.1242/jcs.107.3.387
/ J Cell Sci / Cytostellin distributes to nuclear regions enriched with splicing factors by Bregman (1994)10.1083/jcb.129.2.287
/ J Cell Biol / Transcriptiondependent redistribution of the large subunit of RNA polymerase II to discrete nuclear domains by Bregman (1995)10.1126/science.8085156
/ Science (Wash DC) / Regulation of alternative splicing in vivo by overexpression of antagonistic splicing factors by Caceres (1994)10.1074/jbc.271.32.19009
/ J Biol Chem / Reversible phosphorylation of the C-terminal domain of RNA polymerase II by Dahmus (1996){'key': '2023072206374530000_B13', 'first-page': '663', 'article-title': 'The superfamily of arginine/serine-rich spliting factors', 'volume': '1', 'author': 'Fu', 'year': '1995', 'journal-title': 'RNA'}
/ RNA / The superfamily of arginine/serine-rich spliting factors by Fu (1995)10.1126/science.1828621
/ Science (Wash DC) / Spliceosomes and snurposomes by Gall (1991)10.1038/374660a0
/ Nature (Lond) / RNA polymerase II C-terminal domain required for enhancer-driven transcription by Gerber (1995)10.1016/0968-0004(93)90016-G
/ Trends Biochem Sci / Positive patches and negative noodles: linking RNA processing to transcription? by Greenleaf (1993){'key': '2023072206374530000_B17'}
10.1016/S0968-0004(00)88977-X
/ Trends Biochem Sci / The RNA polymerase II holoenzyme and its implications for gene regulation by Koleske (1995)10.1016/0962-8924(93)90214-L
/ Trends Cell Biol / The coiled body by Lamond (1993)10.1073/pnas.78.5.2737
/ Proc Natl Acad Sci USA / Monoclonal antibodies to nucleic acid containing cellular constituents: probes for molecular biology and autoimmune disease by Lerner (1981)10.1016/0092-8674(91)90185-2
/ Cell / Arginine/Serine-rich domains of the su(wa) and traRNA processing regulators target proteins to a subnuclear compartment implicated in splicing by Li (1991)10.1083/jcb.121.2.219
/ J Cell Biol / Association of individual hnRNP proteins and snRNPs with nascent transcripts by Matunis (1993)10.1099/0022-1317-75-6-1223
/ J Gen Virol / The nuclear location of PML, a cellular member of the C3HC4 zinc-binding domain protein family, is rearranged during herpes simplex virus infection by the C3HC4 viral protein ICP0 by Maul (1994)10.1016/0092-8674(87)90517-4
/ Cell / Functional redundancy and structural polymorphism in the large subunit of RNA polymerase II by Nonet (1987)10.1101/gad.9.11.1400
/ Genes Dev / Overexpression of the arginine-rich carboxy-terminal region of U1 snRNP 70K inhibits both splicing and nucleocytoplasmic transport of mRNA by Romac (1995)10.1083/jcb.115.3.587
/ J Cell Biol / A conserved family of nuclear phosphoproteins localized to sites of polymerase II transcription by Roth (1991){'key': '2023072206374530000_B27'}
10.1038/347491a0
/ Nature (Lond) / RNA polymerase II C-terminal repeat influences response to transcriptional enhancer signals by Scafe (1990)10.1016/0092-8674(94)90130-9
/ Cell / Split genes and RNA splicing by Sharp (1994){'key': '2023072206374530000_B30', 'first-page': '1590', 'article-title': 'PML nuclear bodies are general targets for inflammation and cell proliferation', 'volume': '55', 'author': 'Terris', 'year': '1995', 'journal-title': 'Cancer Res'}
/ Cancer Res / PML nuclear bodies are general targets for inflammation and cell proliferation by Terris (1995)10.1242/jcs.103.2.381
/ J Cell Sci / Cytostellin: a novel, highly conserved protein that undergoes continuous redistribution during the cell cycle by Warren (1992)10.1093/nar/20.4.910
/ Nucleic Acids Res / Complete sequence of the human RNA polymerase II largest subunit by Wintzerith (1992)10.1126/science.8446901
/ Science (Wash DC) / Higher level organization of individual gene transcription and RNA splicing by Xing (1993)10.1083/jcb.131.6.1635
/ J Cell Biol / Nonrandom gene organization: structural arrangements of specific pre-mRNA transcription and splicing with SC–35 domains by Xing (1995)10.1073/pnas.93.14.6975
/ Proc Natl Acad Sci USA / The CTD of RNA polymerase II interacts with a novel set of SR-like proteins by Yuryev (1996){'key': '2023072206374530000_B36'}
10.1073/pnas.85.11.3698
/ Proc Natl Acad Sci USA / The C-terminal repeat domain of RNA polymerase II largest subunit is essential in vivo but is not required for accurate transcription initiation in vitro. by Zehring (1988)10.1038/372809a0
/ Nature (Lond) / Localization of pre-mRNA splicing in mammalian nuclei by Zhang (1994)
Dates
Type | When |
---|---|
Created | 23 years ago (July 26, 2002, 12:46 p.m.) |
Deposited | 2 years, 1 month ago (July 22, 2023, 2:39 a.m.) |
Indexed | 1 month, 3 weeks ago (July 2, 2025, 2:31 p.m.) |
Issued | 28 years, 7 months ago (Jan. 13, 1997) |
Published | 28 years, 7 months ago (Jan. 13, 1997) |
Published Online | 28 years, 7 months ago (Jan. 13, 1997) |
Published Print | 28 years, 7 months ago (Jan. 13, 1997) |
@article{Du_1997, title={A Functional Interaction between the Carboxy-Terminal Domain of RNA Polymerase II and Pre-mRNA Splicing}, volume={136}, ISSN={1540-8140}, url={http://dx.doi.org/10.1083/jcb.136.1.5}, DOI={10.1083/jcb.136.1.5}, number={1}, journal={The Journal of Cell Biology}, publisher={Rockefeller University Press}, author={Du, Lei and Warren, Stephen L.}, year={1997}, month=jan, pages={5–18} }