Abstract
Messenger RNA is produced by RNA polymerase II (pol II) transcription, followed by processing of the primary transcript. Transcription, splicing and cleavage–polyadenylation can occur independently in vitro, but we demonstrate here that these processes are intimately linked in vivo. We show that the carboxy-terminal domain (CTD) of the pol II large subunit is required for efficient RNA processing. Splicing, processing of the 3′ end and termination of transcription downstream of the poly(A) site, are all inhibited by truncation of the CTD. We found that the cleavage–polyadenylation factors CPSF and CstF specifically bound to CTD affinity columns and copurified with pol II in a high-molecular-mass complex. Our demonstration of an association between the CTD and 3′-processing factors, considered together with reports of a similar interaction with splicing factors1,2, suggests that an mRNA 'factory' exists which carries out coupled transcription, splicing and cleavage–polyadenylation of mRNA precursors.
This is a preview of subscription content, access via your institution
Access options
Subscribe to this journal
Receive 51 print issues and online access
$199.00 per year
only $3.90 per issue
Buy this article
- Purchase on Springer Link
- Instant access to full article PDF
Prices may be subject to local taxes which are calculated during checkout
Similar content being viewed by others
References
Yuryev, A. et al. Proc. Natl Acad. Sci. USA 93, 6975–6980 (1996).
Mortillaro, M. J. et al. Proc. Natl Acad. Sci. USA 93, 8253–8257 (1996).
Gerber, H. P. et al. Nature 374, 660–662 (1995).
Zehring, W. A., Lee, J. M., Weeks, J. R., Jokerst, R. S. & Greenleaf, A. L. Proc. Natl Acad. Sci. USA 85, 3698–3702 (1988).
Nesic, D., Cheng, J. & Maquat, L. E. Mol. Cell. Biol. 13, 3359–3369 (1993).
Niwa, M., Rose, S. D. & Berget, S. M. Genes Dev. 4, 1552–1559 (1990).
Connelly, S. & Manley, J. L. Genes Dev. 2, 440–452 (1988).
Logan, J., Falck, P. E., Darnell, J. E. J. & Shenk, T. Proc. Natl Acad. Sci. USA 84, 8306–8310 (1987).
Whitelaw, E. & Proudfoot, N. EMBO J. 5, 2915–2922 (1986).
Usheva, A. et al. Cell 69, 871–881 (1992).
Takagaki, Y. & Manley, J. L. J. Biol. Chem. 267, 23471–23474 (1992).
Ossipow, V., Tassan, J. P., Nigg, E. A. & Schibler, U. Cell 83, 137–146 (1995).
Maldonado, E. et al. Nature 381, 86–89 (1996).
Smale, S. T. & Tijan, R. Mol. Cell. Biol. 5, 5352–5362 (1985).
Sisodia, S. S., Sollner, W. B. & Cleveland, D. W. Mol. Cell. Biol. 7, 3602–3612 (1987).
Mifflin, R. C. & Kellems, R. E. J. Biol. Chem. 266, 19593–19598 (1991).
Greenleaf, A. L. Trends Biochem. Sci. 18, 117–119 (1993).
Beyer, A. L. & Osheim, Y. N. Genes Dev. 2, 754–765 (1988).
Wuarin, J. & Schibler, U. Mol. Cell Biol. 14, 7219–7225 (1994).
Lutz, C. S. et al. Genes Dev. 10, 325–337 (1996).
Boelens, W. C. et al. Cell 72, 881–892 (1993).
Zhang, G., Taneja, K. L., Singer, R. H. & Green, M. R. Nature 372, 809–812 (1994).
Mattaj, I. W. Nature 372, 727–728 (1994).
Schul, W. et al. EMBO J. 15, 2883–2892 (1996).
Blau, J. et al. Mol. Cell. Biol. 16, 2044–2055 (1996).
Lieber, A., Kiessing, U. & Strauss, M. Nucleic Acids Res. 17, 8485–8493 (1989).
West, M. & Corden, J. Genetics 140, 1223–1233 (1995).
Peterson, S. R., Dvir, A., Anderson, C. W. & Dynan, W. S. Genes Dev. 6, 426–438 (1992).
Dignam, J. D., Lebovitz, R. M. & Roeder, R. G. Nucleic Acids Res. 11, 1475–1489 (1983).
Jenny, A., Minvielle-Bastia, L., Preker, P. & Keller, W. Science 274, 1514–1517 (1996).
Author information
Authors and Affiliations
Rights and permissions
About this article
Cite this article
McCracken, S., Fong, N., Yankulov, K. et al. The C-terminal domain of RNA polymerase II couples mRNA processing to transcription. Nature 385, 357–361 (1997). https://doi.org/10.1038/385357a0
Received:
Accepted:
Issue Date:
DOI: https://doi.org/10.1038/385357a0
This article is cited by
-
Enzymatically amplified linear dbDNATM as a rapid and scalable solution to industrial lentiviral vector manufacturing
Gene Therapy (2023)
-
CCIVR2 facilitates comprehensive identification of both overlapping and non-overlapping antisense transcripts within specified regions
Scientific Reports (2023)
-
CSTF2 mediated mRNA N6-methyladenosine modification drives pancreatic ductal adenocarcinoma m6A subtypes
Nature Communications (2023)
-
Alternative polyadenylation by sequential activation of distal and proximal PolyA sites
Nature Structural & Molecular Biology (2022)
-
Context-specific regulation and function of mRNA alternative polyadenylation
Nature Reviews Molecular Cell Biology (2022)
Comments
By submitting a comment you agree to abide by our Terms and Community Guidelines. If you find something abusive or that does not comply with our terms or guidelines please flag it as inappropriate.