Proteomic analysis of murine Piwi proteins reveals a role for arginine methylation in specifying interaction with Tudor family members

Vagin, V. V., Wohlschlegel, J., Qu, J., Jonsson, Z., Huang, X., Chuma, S., Girard, A., Sachidanandam, R., Hannon, G. J., Aravin, A. A. (2009) Proteomic analysis of murine Piwi proteins reveals a role for arginine methylation in specifying interaction with Tudor family members. Genes and Development, 23 (15). pp. 1749-1762. ISSN 08909369 (ISSN)

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Abstract

In germ cells, Piwi proteins interact with a specific class of small noncoding RNAs, piwi-interacting RNAs (piRNAs). Together, these form a pathway that represses transposable elements, thus safeguarding germ cell genomes. Basic models describe the overall operation of piRNA pathways. However, the protein compositions of Piwi complexes, the critical protein-protein interactions that drive small RNA production and target recognition, and the precise molecular consequences of conserved localization to germline structures, call nuage, remains poorly understood.We purified the three murine Piwi family proteins, MILI, MIWI, and MIWI2, from mouse germ cells and characterized their interacting protein partners. Piwi proteins were found in complex with PRMT5/WDR77, an enzyme that dimethylates arginine residues. By immunoprecipitation with specific antibodies and by mass spectrometry, we found that Piwi proteins are arginine methylated at conserved positions in their N termini. These modifications are essential to direct complex formation with specific members of the Tudor protein family. Recognition of methylarginine marks by Tudor proteins can drive the localization of Piwi proteins to cytoplasmic foci in an artificial setting, supporting a role for this interaction in Piwi localization to nuage, a characteristic that correlates with proper operation of the piRNA pathway and transposon silencing in multiple organisms. © 2009 by Cold Spring Harbor Laboratory Press.

Item Type: Paper
Uncontrolled Keywords: Arginine methyation piRNAs Transposon silencing Tudor proteins Piwi protein protein protein mili protein miwi protein miwi2 protein prmt5 protein tudor protein wdr77 unclassified drug animal cell animal tissue article controlled study immunoprecipitation mass spectrometry mouse nonhuman priority journal protein analysis protein methylation protein protein interaction proteomics Animals Arginine Cell Line DNA Transposable Elements Humans Male Methylation Mice Protein Methyltransferases Proteins Ribonucleoproteins Ribonucleoproteins, Small Nuclear Testis Murinae
Subjects: bioinformatics > genomics and proteomics
bioinformatics > genomics and proteomics > genetics & nucleic acid processing > protein structure, function, modification > protein types > Piwi protein
bioinformatics > genomics and proteomics > genetics & nucleic acid processing > protein structure, function, modification
bioinformatics > genomics and proteomics > genetics & nucleic acid processing > protein structure, function, modification > protein types > serine arginine rich proteins
CSHL Authors:
Communities: CSHL Post Doctoral Fellows
CSHL labs > Hannon lab
School of Biological Sciences > Publications
Depositing User: Matt Covey
Date: 2009
Date Deposited: 09 Jan 2013 16:44
Last Modified: 26 Sep 2014 19:17
PMCID: PMC2720255
Related URLs:
URI: https://repository.cshl.edu/id/eprint/26434

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