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Binding of guide piRNA triggers methylation of the unstructured N-terminal region of Aub leading to assembly of the piRNA amplification complex

Huang, Xiawei and Hu, Hongmiao and Webster, Alexandre and Zou, Fan and Du, Jiamu and Fejes Tóth, Katalin and Aravin, Alexei A. and Li, Sisi (2020) Binding of guide piRNA triggers methylation of the unstructured N-terminal region of Aub leading to assembly of the piRNA amplification complex. . (Unpublished) https://resolver.caltech.edu/CaltechAUTHORS:20200715-143612345

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Abstract

Piwi proteins use guide piRNAs to repress selfish genomic elements, protecting the genomic integrity of gametes and ensuring the fertility of animal species. Efficient transposon repression depends on amplification of piRNA guides in the ping-pong cycle, which in Drosophila entails tight cooperation between two Piwi proteins, Aub and Ago3. Here we show that post-translational modification, symmetric dimethylarginine (sDMA), of Aub is essential for piRNA biogenesis, transposon silencing and fertility. Methylation is triggered by loading of a piRNA guide into Aub, which exposes its unstructured N-terminal region to the PRMT5 methylosome complex. Thus, sDMA modification is a signal that Aub is loaded with piRNA guide. Amplification of piRNA in the ping-pong cycle requires assembly of a tertiary complex scaffolded by Krimper, which simultaneously binds the N-terminal regions of Aub and Ago3. To promote generation of new piRNA, Krimp uses its two Tudor domains to bind Aub and Ago3 in opposite modification and piRNA-loading states. Our results reveal that post-translational modifications in unstructured regions of Piwi proteins and their binding by Tudor domains that are capable of discriminating between modification states is essential for piRNA biogenesis and silencing.


Item Type:Report or Paper (Discussion Paper)
Related URLs:
URLURL TypeDescription
https://doi.org/10.1101/2020.07.14.203323DOIDiscussion Paper
ORCID:
AuthorORCID
Fejes Tóth, Katalin0000-0001-6558-2636
Aravin, Alexei A.0000-0002-6956-8257
Additional Information:The copyright holder for this preprint is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. It is made available under a CC-BY-NC-ND 4.0 International license. Posted July 14, 2020. We thank members of the Aravin lab for discussion and comments. We thank the BL19U1 beamlines staff at the Shanghai Synchrotron Radiation Facility for assistance during data collection. We thank Igor Antoshechkin (Caltech) for help with sequencing. This work was supported by grants from the National Institutes of Health (R01 GM097363) and by the HHMI Faculty Scholar Award to A.A.A. and the National Natural Science Foundation of China (31870755) and the Guangdong Innovation Research Team Fund (2016ZT06S172) to S.L. Data availability: Small RNA-seq data are available on the GEO database, GSE153156. X-ray structures have been deposited in the RCSB Protein Data Bank with the accession codes: 7CFB for the eTud1 apo structure, 7CFC for the eTud1-Ago3 complex structure and 7CFD for the eTud2-AubR15me2 structure.
Funders:
Funding AgencyGrant Number
NIHR01 GM097363
Howard Hughes Medical Institute (HHMI)UNSPECIFIED
National Natural Science Foundation of China31870755
Guangdong Innovation Research Team Fund2016ZT06S172
Record Number:CaltechAUTHORS:20200715-143612345
Persistent URL:https://resolver.caltech.edu/CaltechAUTHORS:20200715-143612345
Official Citation:Binding of guide piRNA triggers methylation of the unstructured N-terminal region of Aub leading to assembly of the piRNA amplification complex. Xiawei Huang, Hongmiao Hu, Alexandre Webster, Fan Zou, Jiamu Du, Katalin Fejes Toth, Alexei Aravin, Sisi Li. bioRxiv 2020.07.14.203323; doi: https://doi.org/10.1101/2020.07.14.203323
Usage Policy:No commercial reproduction, distribution, display or performance rights in this work are provided.
ID Code:104390
Collection:CaltechAUTHORS
Deposited By: Tony Diaz
Deposited On:15 Jul 2020 21:50
Last Modified:15 Jul 2020 21:50

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