title: Allosteric regulation of human poly(A)-specific ribonuclease by cap and potassium ions.
abstract: Poly(A)-specific ribonuclease (PARN), a multi-domain dimeric enzyme, is a deadenylase in higher vertebrates and plants with the unique property of cap-dependent catalysis and processivity. We found that PARN is an allosteric enzyme, and potassium ions and the cap analogue were effectors with binding sites located at the RRM domain. The binding of K(+) to the entire RRM domain led to an increase of substrate-binding affinity but a decrease in the cooperativity of the substrate-binding site, while the binding of the cap analogue decreased both the catalytic efficiency and the substrate-binding affinity. The dissimilar kinetic properties of the enzymes with and without the entire RRM domain suggested that the RRM domain played a central role in the allosteric communications of PARN regulation. The allostery is proposed to be important to the multi-level regulation of PARN to achieve precise control of the mRNA poly(A) tail length.
authors.affiliation: State Key Laboratory of Biomembrane and Membrane Biotechnology, Department of Biological Sciences and Biotechnology, Tsinghua University, Beijing 100084, China.
authors.forename: Wei-Feng
authors.initials: WF
authors.lastname: Liu
authors.forename: Ao
authors.initials: A
authors.lastname: Zhang
authors.forename: Yuan
authors.initials: Y
authors.lastname: Cheng
authors.forename: Hai-Meng
authors.initials: HM
authors.lastname: Zhou
authors.forename: Yong-Bin
authors.initials: YB
authors.lastname: Yan
mesh_terms: D000494:Allosteric Regulation; D001665:Binding Sites; D002414:Cations, Monovalent / Q000378:metabolism; D005095:Exoribonucleases / Q000737:chemistry / Q000378:metabolism*; D006801:Humans; D011188:Potassium / Q000737:chemistry / Q000378:metabolism*; D017434:Protein Structure, Tertiary; D012315:RNA Caps / Q000737:chemistry / Q000378:metabolism*; D012333:RNA, Messenger / Q000378:metabolism
chemical_list: D002414:Cations, Monovalent; D005095:Exoribonucleases; D011188:Potassium; D012315:RNA Caps; D012333:RNA, Messenger