DOI: 10.1073/pnas.94.22.11893. Participation of the nuclear cap binding complex in pre-mRNA 3′ processing

Participation of the nuclear cap binding complex in pre-mRNA 3′ processing

10.1073/pnas.94.22.11893

Crossref journal-article

Proceedings of the National Academy of Sciences

Proceedings of the National Academy of Sciences (341)

Abstract

Communication between the 5′ and 3′ ends is a common feature of several aspects of eukaryotic mRNA metabolism. In the nucleus, the pre-mRNA 5′ end is bound by the nuclear cap binding complex (CBC). This RNA–protein complex plays an active role in both splicing and RNA export. We provide evidence for participation of CBC in the processing of the 3′ end of the message. Depletion of CBC from HeLa cell nuclear extract strongly reduced the endonucleolytic cleavage step of the cleavage and polyadenylation process. Cleavage was restored by addition of recombinant CBC. CBC depletion was found to reduce the stability of poly(A) site cleavage complexes formed in nuclear extract. We also provide evidence that the communication between the 5′ and 3′ ends of the pre-mRNA during processing is mediated by the physical association of the CBC/cap complex with 3′ processing factors bound at the poly(A) site. These observations, along with previous data on the function of CBC in splicing, illustrate the key role played by CBC in pre-mRNA recognition and processing. The data provides further support for the hypothesis that pre-mRNAs and mRNAs may exist and be functional in the form of “closed-loops,” due to interactions between factors bound at their 5′ and 3′ ends.

Bibliography

Flaherty, S. M., Fortes, P., Izaurralde, E., Mattaj, I. W., & Gilmartin, G. M. (1997). Participation of the nuclear cap binding complex in pre-mRNA 3â²âprocessing. Proceedings of the National Academy of Sciences, 94(22), 11893â11898.

Authors 5

Sean M. Flaherty (first)
Puri Fortes (additional)
Elisa Izaurralde (additional)
Iain W. Mattaj (additional)
Gregory M. Gilmartin (additional)

References 54 Referenced 176

10.1073/pnas.90.17.7923
10.1016/0092-8674(80)90389-X
10.1016/0092-8674(94)90130-9
10.1016/0092-8674(95)90001-2
10.1016/0167-4781(94)00248-2
10.1016/S0021-9258(18)55058-4
10.1016/S0021-9258(18)42111-4
10.1101/gad.4.12a.2112
10.1101/gad.3.12b.2180
10.1101/gad.3.11.1711
10.1038/353229a0
10.1016/S0021-9258(18)49964-4
10.1002/j.1460-2075.1993.tb05690.x
10.1101/gad.3.9.1401
10.1074/jbc.270.6.2800
10.1016/0092-8674(85)90240-5
10.1101/gad.2.5.578
10.1128/MCB.16.6.2579
10.1101/gad.10.13.1699
10.1101/gad.10.13.1683
10.1093/nar/24.17.3332
10.1073/pnas.84.15.5187
10.1083/jcb.118.6.1287
10.1016/0092-8674(94)90530-4
10.1038/376709a0
10.1093/nar/23.18.3638
10.1093/nar/18.23.6989
10.1016/S0092-8674(00)81319-7
10.1016/0092-8674(92)90224-Z
10.1101/gad.5.11.2108
10.1002/j.1460-2075.1995.tb00320.x
10.1002/j.1460-2075.1996.tb01108.x
10.1038/382642a0
E Wahle, W Keller RNA Processing: A Practical Approach, eds S J Higgins, B D Hames (Oxford Univ. Press, Oxford) II, 1–33 (1994). / RNA Processing: A Practical Approach by Wahle E (1994)
10.1101/gad.9.1.72
10.1016/0092-8674(91)90502-P
10.1002/j.1460-2075.1992.tb05542.x
10.1002/j.1460-2075.1991.tb07938.x
10.1016/S0021-9258(18)42423-4
10.1128/mcb.14.7.4682-4693.1994
10.1128/mcb.13.6.3359-3369.1993
10.1101/gad.8.3.363
10.1101/gad.4.9.1552
10.1074/jbc.270.6.2411
10.1101/gad.11.6.761
10.1016/0092-8674(93)90577-D
Gunderson S. I. Beyer K. Martin G. Keller W. Boelens W. C. & Mattaj I. W. (1994) Cell 531–541. (10.1016/0092-8674(94)90116-3)
10.1101/gad.10.3.325
10.1101/gad.10.2.208
10.1038/385357a0
10.1083/jcb.133.1.5
10.1002/j.1460-2075.1996.tb01108.x
10.1101/gad.9.19.2421
A Jacobson Translational Control, eds J W B Hershey, M B Matthews, N Sonenberg (Cold Spring Harbor Lab. Press, Plainview, NY), pp. 451–480 (1996). / Translational Control by Jacobson A (1996)

Dates

Type	When
Created	23 years, 1 month ago (July 26, 2002, 10:44 a.m.)
Deposited	3 years, 4 months ago (April 13, 2022, 3:18 p.m.)
Indexed	3 weeks, 3 days ago (Aug. 6, 2025, 8:25 a.m.)
Issued	27 years, 10 months ago (Oct. 28, 1997)
Published	27 years, 10 months ago (Oct. 28, 1997)
Published Online	27 years, 10 months ago (Oct. 28, 1997)
Published Print	27 years, 10 months ago (Oct. 28, 1997)

Funders 0

None

BibTeX

@article{Flaherty_1997, title={Participation of the nuclear cap binding complex in pre-mRNA 3′ processing}, volume={94}, ISSN={1091-6490}, url={http://dx.doi.org/10.1073/pnas.94.22.11893}, DOI={10.1073/pnas.94.22.11893}, number={22}, journal={Proceedings of the National Academy of Sciences}, publisher={Proceedings of the National Academy of Sciences}, author={Flaherty, Sean M. and Fortes, Puri and Izaurralde, Elisa and Mattaj, Iain W. and Gilmartin, Gregory M.}, year={1997}, month=oct, pages={11893–11898} }

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