title: Recognition of adenosine residues by the active site of poly(A)-specific ribonuclease.
abstract: Poly(A)-specific ribonuclease (PARN) is a mammalian 3'-exoribonuclease that degrades poly(A) with high specificity. To reveal mechanisms by which poly(A) is recognized by the active site of PARN, we have performed a kinetic analysis using a large repertoire of trinucleotide substrates. Our analysis demonstrated that PARN harbors specificity for adenosine recognition in its active site and that the nucleotides surrounding the scissile bond are critical for adenosine recognition. We propose that two binding pockets, which interact with the nucleotides surrounding the scissile bond, play a pivotal role in providing specificity for the recognition of adenosine residues by the active site of PARN. In addition, we show that PARN, besides poly(A), also quite efficiently degrades poly(U), approximately 10-fold less efficiently than poly(A). The poly(U)-degrading property of PARN could be of biological significance as oligo(U) tails recently have been proposed to play a role in RNA stabilization and destabilization.
authors.affiliation: Department of Cell and Molecular Biology, Uppsala University, Box 596, SE-751 24 Uppsala, Sweden.
authors.forename: Niklas
authors.initials: N
authors.lastname: Henriksson
authors.forename: Per
authors.initials: P
authors.lastname: Nilsson
authors.forename: Mousheng
authors.initials: M
authors.lastname: Wu
authors.forename: Haiwei
authors.initials: H
authors.lastname: Song
authors.forename: Anders
authors.initials: A
authors.lastname: Virtanen
mesh_terms: D000241:Adenosine / Q000378:metabolism*; D000596:Amino Acids / Q000378:metabolism; D001704:Biopolymers / Q000378:metabolism; D020134:Catalytic Domain; D005095:Exoribonucleases / Q000737:chemistry* / Q000378:metabolism*; D006801:Humans; D007700:Kinetics; D009711:Nucleotides / Q000378:metabolism; D011061:Poly A / Q000378:metabolism; D020871:RNA Stability; D013379:Substrate Specificity
chemical_list: D000241:Adenosine; D000596:Amino Acids; D001704:Biopolymers; D005095:Exoribonucleases; D009711:Nucleotides; D011061:Poly A