Article
- The EMBO Journal (2004) 23, 616 - 626
- doi:10.1038/sj.emboj.7600070
Published online: 29 January 2004
Subject Category:
Human Fip1 is a subunit of CPSF that binds to U-rich RNA elements and stimulates poly(A) polymerase
Isabelle Kaufmann1, Georges Martin1, Arno Friedlein2, Hanno Langen2 and Walter Keller1
- Department of Cell Biology, Biozentrum, University of Basel, Basel, Switzerland
- Roche Genetics, F Hoffmann-La Roche Ltd, Basel, Switzerland
Correspondence to:
Walter Keller, Department of Cell Biology, Biozentrum, University of Basel, Klingelbergstrasse 70, CH-4056 Basel, Switzerland. Tel.: +41 61 267 20 60; Fax: +41 61 267 20 79; E-mail: walter.keller@unibas.ch
Received 18 August 2003; Accepted 17 December 2003
Abstract
In mammals, polyadenylation of mRNA precursors (pre-mRNAs) by poly(A) polymerase (PAP) depends on cleavage and polyadenylation specificity factor (CPSF). CPSF is a multisubunit complex that binds to the canonical AAUAAA hexamer and to U-rich upstream sequence elements on the pre-mRNA, thereby stimulating the otherwise weakly active and nonspecific polymerase to elongate efficiently RNAs containing a poly(A) signal. Based on sequence similarity to the Saccharomyces cerevisiae polyadenylation factor Fip1p, we have identified human Fip1 (hFip1) and found that the protein is an integral subunit of CPSF. hFip1 interacts with PAP and has an arginine-rich RNA-binding motif that preferentially binds to U-rich sequence elements on the pre-mRNA. Recombinant hFip1 is sufficient to stimulate the in vitro polyadenylation activity of PAP in a U-rich element-dependent manner. hFip1, CPSF160 and PAP form a ternary complex in vitro, suggesting that hFip1 and CPSF160 act together in poly(A) site recognition and in cooperative recruitment of PAP to the RNA. These results show that hFip1 significantly contributes to CPSF-mediated stimulation of PAP activity.
Keywords:
- cleavage and polyadenylation specificity factor,
- polyadenylation,
- poly(A) site recognition,
- pre-mRNA 3' end processing,
- upstream sequence elements
MORE ARTICLES LIKE THIS
These links to content published by NPG are automatically generated
NEWS AND VIEWS
RNA processing A tale of two tails
Nature News and Views (03 Sep 1998)
Nature Structural & Molecular Biology News and Views (01 Dec 2004)
RESEARCH
Improving Transcriptional Termination of Self-inactivating Gamma-retroviral and Lentiviral Vectors
Molecular Therapy Original Article
Crystal structure of mammalian poly(A) polymerase in complex with an analog of ATP
The EMBO Journal Article (15 Aug 2000)
