A functional deadenylation assay identifies human CUG-BP as a deadenylation factor.
CUG-BP is a human nuclear and cytoplasmic RNA-binding protein. A role in the control of alternative splicing has been reported, but to date no cytoplasmic function for this protein has been demonstrated. A close sequence homolog of CUG-BP is EDEN-BP that is required for the specific cytoplasmic poly(A) tail shortening of certain mRNAs after fertilization of Xenopus eggs. Here, we show that human CUG-BP and Xenopus EDEN-BP have very similar RNA-binding specificities. In addition, we use a deadenylation assay to show that CUG-BP is able to act as a deadenylation factor. In contrast, a mutant form of CUG-BP, though still able to bind to RNA with a specificity similar to that of wild-type CUG-BP, does not act as a deadenylation factor. It is suggested that the CUG expansion associated with Type 1 myotonic dystrophy can affect the function or the activity of CUG-BP, leading to a trans-dominant effect on normal RNA processing. The results presented here identify CUG-BP-dependent deadenylation as a potential cytoplasmic target for this trans-dominant effect.
Paillard
Luc
L
CNRS UMR 6061, Faculté de Médecine, Université Rennes 1, 2, avenue Léon-Bernard, CS 34317, 35043 cedex, Rennes, France. Luc.Paillard@univ-rennes1.fr
Legagneux
Vincent
V
Beverley Osborne
H
H
D000067879:CELF1 Protein; D003593:Cytoplasm / Q000378:metabolism; D006801:Humans; D007700:Kinetics; D009223:Myotonic Dystrophy / Q000235:genetics; D011061:Poly A / Q000378:metabolism*; D012323:RNA Processing, Post-Transcriptional; D020871:RNA Stability; D016601:RNA-Binding Proteins / Q000378:metabolism / Q000502:physiology*; D013379:Substrate Specificity; D019680:Trinucleotide Repeat Expansion; D029867:Xenopus Proteins
D000067879:CELF1 Protein; C102843:CELF1 protein, human; C110462:EDEN-specific RNA-binding protein, Xenopus; D016601:RNA-Binding Proteins; D029867:Xenopus Proteins; D011061:Poly A