Recognition of Adenosine Residues by the Active Site of Poly(A)-specific Ribonuclease |
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Authors: | Niklas Henriksson Per Nilsson Mousheng Wu Haiwei Song Anders Virtanen |
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Institution: | From the ‡Department of Cell and Molecular Biology, Uppsala University, Box 596, SE-751 24 Uppsala, Sweden and ;the §Institute of Molecular and Cell Biology, 61 Biopolis Drive, Proteos, Singapore 138673 |
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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), ~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. |
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Keywords: | RNA/Messenger RNA/mRNA RNA/Metabolism RNA/Processing RNA/Turnover Deadenylation mRNA Degradation mRNA Poly(A) Tail |
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