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.
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.
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.
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.
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.
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.
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.