Structural insight into poly(A) binding and catalytic mechanism of human PARN

• Published in: The EMBO journal 2005-12, Vol.24 (23), p.4082-4093
• Main Authors: Wu, Mousheng, Reuter, Michael, Lilie, Hauke, Liu, Yuying, Wahle, Elmar, Song, Haiwei
• Format: Article
• Language: English
• Subjects: Adenosine - metabolism; Amino Acid Sequence; Catalytic Domain; Crystallography, X-Ray; deadenylation; Dimerization; EMBO36; EMBO40; Exoribonucleases - chemistry; Exoribonucleases - metabolism; Humans; Molecular Sequence Data; mRNA decay; Mutation; PARN; Polymers - metabolism; processivity; Protein Binding; Protein Structure, Tertiary; Sequence Alignment; Structural Homology, Protein; X-ray crystallography
• ISSN: 0261-4189; 1460-2075
• DOI: 10.1038/sj.emboj.7600869

Poly(A)‐specific ribonuclease (PARN) is a processive, poly(A)‐specific 3′ exoribonuclease. The crystal structure of C‐terminal truncated human PARN determined in two states (free and RNA‐bound forms) reveals that PARNn is folded into two domains, an R3H domain and a nuclease domain similar to those of Pop2p and ε186. The high similarity of the active site structures of PARNn and ε186 suggests that they may have a similar catalytic mechanism. PARNn forms a tight homodimer, with the R3H domain of one subunit partially enclosing the active site of the other subunit and poly(A) bound in a deep cavity of its nuclease domain in a sequence‐nonspecific manner. The R3H domain and, possibly, the cap‐binding domain are involved in poly(A) binding but these domains alone do not appear to contribute to poly(A) specificity. Mutations disrupting dimerization abolish both the enzymatic and RNA‐binding activities, suggesting that the PARN dimer is a structural and functional unit. The cap‐binding domain may act in concert with the R3H domain to amplify the processivity of PARN.