The RRM domain of poly(A)-specific ribonuclease has a noncanonical binding site for mRNA cap analog recognition

  • The degradation of the poly(A) tail is crucial for posttranscriptional gene regulation and for quality control of mRNA. Poly(A)-specific ribonuclease (PARN) is one of the major mammalian 3’ specific exo-ribonucleases involved in the degradation of the mRNA poly(A) tail, and it is also involved in the regulation of translation in early embryonic development. The interaction between PARN and the m7GpppG cap of mRNA plays a key role in stimulating the rate of deadenylation. Here we report the solution structures of the cap-binding domain of mouse PARN with and without the m7GpppG cap analog. The structure of the cap-binding domain adopts the RNA recognition motif (RRM) with a characteristic a-helical extension at its C-terminus, which covers the b-sheet surface (hereafter referred to as PARN RRM). In the complex structure of PARN RRM with the cap analog, the base of the N7-methyl guanosine (m7G) of the cap analog stacks with the solvent-exposed aromatic side chain of the distinctive tryptophan residue 468, located at the C-terminal end of the second b-strand. These unique structural features in PARN RRM reveal a novel cap-binding mode, which is distinct from the nucleotide recognition mode of the canonical RRM domains.

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Author:Takashi Nagata, Sakura Suzuki, Ryuta Endo, Mikako Shirouzu, Takaho Terada, Makoto Inoue, Takanori Kigawa, Naohiro Kobayashi, Peter GüntertORCiDGND, Akiko Tanaka, Yoshihide Hayashizaki, Yutaka Muto, Shigeyuki Yokoyama
Pubmed Id:
Parent Title (English):Nucleic acids research
Publisher:Oxford Univ. Press
Place of publication:Oxford
Document Type:Article
Date of Publication (online):2008/09/25
Date of first Publication:2008/07/19
Publishing Institution:Universitätsbibliothek Johann Christian Senckenberg
Release Date:2008/09/25
Tag:binding sites; catabolism; embryologic development; gene expression regulation; guanosine; helix (snails); mammals; messenger; mice; multiple sclerosis; nucleotides; quality control; relapsing-remitting; ribonucleases; rna; rna recognition motif; solvents; titration method; tryptophan
Page Number:15
First Page:4754
Last Page:4767
© 2008 The Author(s) This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License ( by-nc/2.0/uk/) which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.
Source:Nucleic Acids Research, 2008, Vol. 36, No. 14, 4754–4767 Published online 19 July 2008 doi:10.1093/nar/gkn458 ; This article is part of the following issue: "Supplementary Data",
Institutes:Biochemie, Chemie und Pharmazie / Biochemie und Chemie
Wissenschaftliche Zentren und koordinierte Programme / Zentrum für Biomolekulare Magnetische Resonanz (BMRZ)
Dewey Decimal Classification:5 Naturwissenschaften und Mathematik / 57 Biowissenschaften; Biologie / 570 Biowissenschaften; Biologie
Sammlungen:Sammlung Biologie / Sondersammelgebiets-Volltexte
Licence (German):License LogoCreative Commons - Namensnennung-Nicht kommerziell 2.0