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Phosphorylation of human Argonaute proteins affects small RNA binding
被引:132
作者:

Ruedel, Sabine
论文数: 0 引用数: 0
h-index: 0
机构:
Max Planck Inst Biochem, CIPSM, Lab RNA Biol, D-82152 Martinsried, Germany
Univ Regensburg, Dept Biochem, Lab RNA Biol, D-93053 Regensburg, Germany Max Planck Inst Biochem, CIPSM, Lab RNA Biol, D-82152 Martinsried, Germany

Wang, Yanli
论文数: 0 引用数: 0
h-index: 0
机构:
Mem Sloan Kettering Canc Ctr, Struct Biol Program, New York, NY 10065 USA Max Planck Inst Biochem, CIPSM, Lab RNA Biol, D-82152 Martinsried, Germany

Lenobel, Rene
论文数: 0 引用数: 0
h-index: 0
机构:
Max Planck Inst Biochem, Dept Cell Biol, D-82152 Martinsried, Germany Max Planck Inst Biochem, CIPSM, Lab RNA Biol, D-82152 Martinsried, Germany

Koerner, Roman
论文数: 0 引用数: 0
h-index: 0
机构:
Max Planck Inst Biochem, Dept Cell Biol, D-82152 Martinsried, Germany Max Planck Inst Biochem, CIPSM, Lab RNA Biol, D-82152 Martinsried, Germany

Hsiao, He-Hsuan
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h-index: 0
机构:
Max Planck Inst Biophys Chem, Bioanalyt Mass Spectrometry Grp, D-37077 Gottingen, Germany Max Planck Inst Biochem, CIPSM, Lab RNA Biol, D-82152 Martinsried, Germany

Urlaub, Henning
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h-index: 0
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Max Planck Inst Biophys Chem, Bioanalyt Mass Spectrometry Grp, D-37077 Gottingen, Germany Max Planck Inst Biochem, CIPSM, Lab RNA Biol, D-82152 Martinsried, Germany

Patel, Dinshaw
论文数: 0 引用数: 0
h-index: 0
机构:
Mem Sloan Kettering Canc Ctr, Struct Biol Program, New York, NY 10065 USA Max Planck Inst Biochem, CIPSM, Lab RNA Biol, D-82152 Martinsried, Germany

Meister, Gunter
论文数: 0 引用数: 0
h-index: 0
机构:
Max Planck Inst Biochem, CIPSM, Lab RNA Biol, D-82152 Martinsried, Germany
Univ Regensburg, Dept Biochem, Lab RNA Biol, D-93053 Regensburg, Germany Max Planck Inst Biochem, CIPSM, Lab RNA Biol, D-82152 Martinsried, Germany
机构:
[1] Max Planck Inst Biochem, CIPSM, Lab RNA Biol, D-82152 Martinsried, Germany
[2] Univ Regensburg, Dept Biochem, Lab RNA Biol, D-93053 Regensburg, Germany
[3] Mem Sloan Kettering Canc Ctr, Struct Biol Program, New York, NY 10065 USA
[4] Max Planck Inst Biochem, Dept Cell Biol, D-82152 Martinsried, Germany
[5] Max Planck Inst Biophys Chem, Bioanalyt Mass Spectrometry Grp, D-37077 Gottingen, Germany
关键词:
AEOLICUS ARGONAUTE;
SILENCING COMPLEX;
CRYSTAL-STRUCTURE;
MESSENGER-RNAS;
MICRORNA;
MIRNAS;
MECHANISMS;
LOCALIZATION;
RECOGNITION;
INHIBITION;
D O I:
10.1093/nar/gkq1032
中图分类号:
Q5 [生物化学];
Q7 [分子生物学];
学科分类号:
071010 ;
081704 ;
摘要:
Argonaute (Ago) proteins are highly conserved between species and constitute a direct-binding platform for small RNAs including short-interfering RNAs (siRNAs), microRNAs (miRNAs) and Piwi interacting RNAs (piRNAs). Small RNAs function as guides whereas Ago proteins are the actual mediators of gene silencing. Although the major steps in RNA-guided gene silencing have been elucidated, not much is known about Ago-protein regulation. Here we report a comprehensive analysis of Ago2 phosphorylation in human cells. We find that the highly conserved tyrosine Y529, located in the small RNA 5'-end-binding pocket of Ago proteins can be phosphorylated. By substituting Y529 with a negatively charged glutamate (E) mimicking a phosphorylated tyrosine, we show that small RNA binding is strongly reduced. Our data suggest that a negatively charged phospho-tyrosine generates a repulsive force that prevents efficient binding of the negatively charged 5' phosphate of the small RNA.
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页码:2330 / 2343
页数:14
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