title: CCR4 and CAF1 deadenylases have an intrinsic activity to remove the post-poly(A) sequence.
abstract: MicroRNAs (miRNAs) recruit the CCR4-NOT complex, which contains two deadenylases, CCR4 and CAF1, to promote shortening of the poly(A) tail. Although both CCR4 and CAF1 generally have a strong preference for poly(A) RNA substrates, it has been reported from yeast to humans that they can also remove non-A residues in vitro to various degrees. However, it remains unknown how CCR4 and CAF1 remove non-A sequences. Herein we show that Drosophila miRNAs can promote the removal of 3'-terminal non-A residues in an exonucleolytic manner, but only if an upstream poly(A) sequence exists. This non-A removing reaction is directly catalyzed by both CCR4 and CAF1 and depends on the balance between the length of the internal poly(A) sequence and that of the downstream non-A sequence. These results suggest that the CCR4-NOT complex has an intrinsic activity to remove the 3'-terminal non-A modifications downstream from the poly(A) tail.
authors.affiliation: Institute of Molecular and Cellular Biosciences, The University of Tokyo, Bunkyo-ku, Tokyo 113-0032, JapanDepartment of Computational Biology and Medical Sciences, The University of Tokyo, Bunkyo-ku, Tokyo 113-0032, Japan.
authors.forename: Sho
authors.initials: S
authors.lastname: Niinuma
authors.affiliation: Institute of Molecular and Cellular Biosciences, The University of Tokyo, Bunkyo-ku, Tokyo 113-0032, JapanDepartment of Computational Biology and Medical Sciences, The University of Tokyo, Bunkyo-ku, Tokyo 113-0032, Japan.
authors.forename: Takashi
authors.initials: T
authors.lastname: Fukaya
authors.affiliation: Institute of Molecular and Cellular Biosciences, The University of Tokyo, Bunkyo-ku, Tokyo 113-0032, JapanDepartment of Computational Biology and Medical Sciences, The University of Tokyo, Bunkyo-ku, Tokyo 113-0032, Japan.
authors.forename: Yukihide
authors.initials: Y
authors.lastname: Tomari
mesh_terms: D000818:Animals; D002352:Carrier Proteins / Q000235:genetics / Q000378:metabolism; D002460:Cell Line; D004330:Drosophila / Q000201:enzymology / Q000235:genetics / Q000378:metabolism; D029721:Drosophila Proteins / Q000235:genetics / Q000378:metabolism*; D035683:MicroRNAs / Q000235:genetics / Q000378:metabolism; D026723:Polyadenylation; D016601:RNA-Binding Proteins; D056505:Retinoblastoma-Binding Protein 4 / Q000235:genetics / Q000378:metabolism*; D012260:Ribonucleases / Q000235:genetics / Q000378:metabolism*
chemical_list: C110251:Caf1-55 protein, Drosophila; D002352:Carrier Proteins; D029721:Drosophila Proteins; D035683:MicroRNAs; C568695:NOT1 protein, Drosophila; D016601:RNA-Binding Proteins; D056505:Retinoblastoma-Binding Protein 4; C501437:CCR4 protein, Drosophila; D012260:Ribonucleases
keywords: CCR4–NOT complex; deadenylase; deadenylation; mRNA decay; microRNA