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Genome protection by germline small RNAs

English title Genome protection by germline small RNAs
Applicant Pillai Ramesh S.
Number 166575
Funding scheme Project funding (Div. I-III)
Research institution Département de Biologie Moléculaire Faculté des Sciences Université de Genève
Institution of higher education University of Geneva - GE
Main discipline Molecular Biology
Start/End 01.06.2016 - 31.05.2019
Approved amount 834'000.00
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All Disciplines (3)

Discipline
Molecular Biology
Biochemistry
Genetics

Keywords (4)

piRNA; Germline; small RNA; transposons

Lay Summary (French)

Lead
Protection de genome par les petite RNA
Lay summary

Les petits ARN ont un rôle conservé dans la régulation de l'expression génique et contrôle de séquences génomiques mobiles appelés éléments transposables. Lignées germinales des animaux expriment une classe spéciale de petits ARN appelé ARN interagissant (Piwi RNAs) qui forment un système dédié contre TE pour assurer l'intégrité du génome et de la fertilité. Nous savons que piRNAs proviennent de 50-100 régions génomiques kb long, mais comment cette long RNA sont transformées en des dizaines de milliers de ~ 24-30 nt piRNAs est
pas connu. Cette proposition examinera comment les cellules germinales désigner à long sequence genomic comme des substrats pour le biogenese de piRNA. Nous allons maintenant examiner ce que ces caractéristiques sont et comment ils sont reconnu. Enfin, nous nous efforcerons de mettre en place in vitro systèmes capables de récapituler piRNA biogenèse de telle sorte que biochimique dissections peuvent être entreprises. Cette proposition prendra une approche interdisciplinaire qui utilisera la biochimie des protéines, cellules biologie, la bioinformatique et des outils de génétique, y compris des lignées de cellules d'insectes et des systèmes de modèles de souris mutante.

Direct link to Lay Summary Last update: 21.04.2016

Responsible applicant and co-applicants

Employees

Publications

Publication
Exonuclease Domain-Containing 1 Enhances MIWI2 piRNA Biogenesis via Its Interaction with TDRD12
Pandey Radha Raman, Homolka David, Olotu Opeyemi, Sachidanandam Ravi, Kotaja Noora, Pillai Ramesh S. (2018), Exonuclease Domain-Containing 1 Enhances MIWI2 piRNA Biogenesis via Its Interaction with TDRD12, in Cell Reports, 24(13), 3423-3432.e4.
Methylation of Structured RNA by the m6A Writer METTL16 Is Essential for Mouse Embryonic Development
Mendel Mateusz, Chen Kuan-Ming, Homolka David, Gos Pascal, Pandey Radha Raman, McCarthy Andrew A., Pillai Ramesh S. (2018), Methylation of Structured RNA by the m6A Writer METTL16 Is Essential for Mouse Embryonic Development, in Molecular Cell, 71(6), 986-1000.e11.
Regulation of m6A Transcripts by the 3→5 RNA Helicase YTHDC2 Is Essential for a Successful Meiotic Program in the Mammalian Germline
Wojtas Magdalena Natalia, Pandey Radha Raman, Mendel Mateusz, Homolka David, Sachidanandam Ravi, Pillai Ramesh S. (2017), Regulation of m6A Transcripts by the 3→5 RNA Helicase YTHDC2 Is Essential for a Successful Meiotic Program in the Mammalian Germline, in Molecular Cell, 68(2), 374-387.e12.
Recruitment of Armitage and Yb to a transcript triggers its phased processing into primary piRNAs in Drosophila ovaries
Pandey Radha Raman, Homolka David, Chen Kuan-Ming, Sachidanandam Ravi, Fauvarque Marie-Odile, Pillai Ramesh S. (2017), Recruitment of Armitage and Yb to a transcript triggers its phased processing into primary piRNAs in Drosophila ovaries, in PLOS Genetics, 13(8), e1006956-e1006956.
Characterization of the mammalian RNA exonuclease 5/NEF-sp as a testis-specific nuclear 3′ → 5′ exoribonuclease
Silva Sara, Homolka David, Pillai Ramesh S. (2017), Characterization of the mammalian RNA exonuclease 5/NEF-sp as a testis-specific nuclear 3′ → 5′ exoribonuclease, in RNA, 23(9), 1385-1392.
Distinct Roles of RNA Helicases MVH and TDRD9 in PIWI Slicing-Triggered Mammalian piRNA Biogenesis and Function
Wenda Joanna M., Homolka David, Yang Zhaolin, Spinelli Pietro, Sachidanandam Ravi, Pandey Radha Raman, Pillai Ramesh S. (2017), Distinct Roles of RNA Helicases MVH and TDRD9 in PIWI Slicing-Triggered Mammalian piRNA Biogenesis and Function, in Developmental Cell, 41(6), 623-637.e9.

Collaboration

Group / person Country
Types of collaboration
Dr. Andrew McCarthy France (Europe)
- in-depth/constructive exchanges on approaches, methods or results
- Publication
Icahn School of Medicine at Sinai United States of America (North America)
- in-depth/constructive exchanges on approaches, methods or results

Scientific events

Active participation

Title Type of contribution Title of article or contribution Date Place Persons involved
Keystone Symposia Noncoding RNAs and RNA-protein interactions, Whistler, Canada, Feb 24-28, 2019 Talk given at a conference Small RNA biogenesis 24.02.2019 Whistler, Canada Pillai Ramesh S.;
Keystone Symposia: Noncoding RNAs: Form, Function, Physiology, Colorado, USA. Feb25-Mar2, 2018 Talk given at a conference Exd1 is a piRNA biogenesis factor 25.02.2018 Colorado, United States of America Pillai Ramesh S.;
FEBS 2017 Meeting, Jerusalem, Israel, 10th-15th Sept, 2017 Talk given at a conference piRNA biogenesis 10.09.2017 Jerusalem, Israel Pillai Ramesh S.;


Associated projects

Number Title Start Funding scheme
186266 Cellular determinants of subthalamic nucleus function 01.06.2019 Sinergia
183529 Multiphoton confocal microscope for multimodal tissue imaging and fluorescence lifetime measurements 01.02.2020 R'EQUIP
185386 Genome protection by germline small RNAs: Biogenesis mechanisms 01.06.2019 Project funding (Div. I-III)
185386 Genome protection by germline small RNAs: Biogenesis mechanisms 01.06.2019 Project funding (Div. I-III)
170794 3D cryo-electron microscopy for analysis of macromolecular assemblies at atomic resolution 01.09.2017 R'EQUIP

Abstract

Small RNAs have a conserved role in regulating gene expression andcontrol of mobile genomic sequences called transposable elements (TEs).Animal germlines express a special class of small RNAs calledPiwi-interacting RNAs (piRNAs) that form a dedicated TE silencing systemto ensure genome integrity and fertility. We know that piRNAs arise from50-100 kb-long genomic regions called piRNA clusters, but how clustertranscripts are processed into tens of thousands of ~24-30 nt piRNAs isnot known. This proposal will examine how germ cells designate longsingle-stranded cluster transcripts as substrates for the piRNAbiogenesis pathway. We present our preliminary data showing that RNAfeatures embedded within the transcripts direct their entry into thepathway. We will now examine what these features are and how they arerecognized. Specifically, how non-conserved (in primary sequence) RNAfeatures are recognized by highly conserved biogenesis machinery. Therole of an exoribonuclease already identified by the lab in Piwicomplexes will be examined. Finally, we will aim to set up in vitrosystems capable of recapitulating piRNA biogenesis so that biochemicaldissections can be undertaken. This proposal will take aninterdisciplinary approach that will use protein biochemistry, cellbiology, bioinformatics and genetics tools including insect cell linesand mouse mutant model systems.
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