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Splicing factors stimulate polyadenylation via USEs at non-canonical 3' end formation signals

Danckwardt, S. and Kaufmann, I. and Gentzel, M. and Foerstner, K. U. and Gantzert, A. -S. and Gehring, N. H. and Neu-Yilik, G. and Bork, P. and Keller, W. and Wilm, M. and Hentze, M. W. and Kulozik, A. E.. (2007) Splicing factors stimulate polyadenylation via USEs at non-canonical 3' end formation signals. The EMBO Journal, 26 (11). pp. 2658-2669.

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Abstract

The prothrombin (F2) 3' end formation signal is highly susceptible to thrombophilia-associated gain-of-function mutations. In its unusual architecture, the F2 3' UTR contains an upstream sequence element (USE) that compensates for weak activities of the non-canonical cleavage site and the downstream U-rich element. Here, we address the mechanism of USE function. We show that the F2 USE contains a highly conserved nonameric core sequence, which promotes 3' end formation in a position- and sequence-dependent manner. We identify proteins that specifically interact with the USE, and demonstrate their function as trans-acting factors that promote 3' end formation. Interestingly, these include the splicing factors U2AF35, U2AF65 and hnRNPI. We show that these splicing factors not only modulate 3' end formation via the USEs contained in the F2 and the complement C2 mRNAs, but also in the biocomputationally identified BCL2L2, IVNS and ACTR mRNAs, suggesting a broader functional role. These data uncover a novel mechanism that functionally links the splicing and 3' end formation machineries of multiple cellular mRNAs in an USE-dependent manner.
Faculties and Departments:05 Faculty of Science > Departement Biozentrum > Former Organization Units Biozentrum > Cell Biology (Keller)
05 Faculty of Science > Departement Biozentrum > Growth & Development
UniBasel Contributors:Keller, Walter
Item Type:Article, refereed
Article Subtype:Research Article
Bibsysno:Link to catalogue
Publisher:Nature Publishing Group
ISSN:0261-4189
e-ISSN:1460-2075
Note:Publication type according to Uni Basel Research Database: Journal article
Language:English
Identification Number:
Last Modified:08 Nov 2017 08:09
Deposited On:22 Mar 2012 13:19

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