Distinct Roles of RNA Helicases MVH and TDRD9 in PIWI Slicing-Triggered Mammalian piRNA Biogenesis and Function

Wenda, J. M., Homolka, D., Yang, Z., Spinelli, P., Sachidanandam, R., Pandey, R. R., Pillai, R. S. (June 2017) Distinct Roles of RNA Helicases MVH and TDRD9 in PIWI Slicing-Triggered Mammalian piRNA Biogenesis and Function. Dev Cell, 41 (6). 623-637.e9. ISSN 1534-5807

Abstract

Small RNAs called PIWI-interacting RNAs (piRNAs) act as an immune system to suppress transposable elements in the animal gonads. A poorly understood adaptive pathway links cytoplasmic slicing of target RNA by the PIWI protein MILI to loading of target-derived piRNAs into nuclear MIWI2. Here we demonstrate that MILI slicing generates a 16-nt by-product that is discarded and a pre-piRNA intermediate that is used for phased piRNA production. The ATPase activity of Mouse Vasa Homolog (MVH) is essential for processing the intermediate into piRNAs, ensuring transposon silencing and male fertility. The ATPase activity controls dissociation of an MVH complex containing PIWI proteins, piRNAs, and slicer products, allowing safe handover of the intermediate. In contrast, ATPase activity of TDRD9 is dispensable for piRNA biogenesis but is essential for transposon silencing and male fertility. Our work implicates distinct RNA helicases in specific steps along the nuclear piRNA pathway.

Item Type: Paper
Uncontrolled Keywords: Ddx4 Mili Miwi Mvh Piwi Spn-E Tdrd9 Vasa piRNAs spermatogenesis
Subjects: 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 > protein types > enzymes > helicase
bioinformatics > genomics and proteomics > genetics & nucleic acid processing > DNA, RNA structure, function, modification > piRNA
CSHL Authors:
Communities: CSHL labs > Vakoc lab
Depositing User: Matt Covey
Date: 19 June 2017
Date Deposited: 21 Jul 2017 19:41
Last Modified: 21 Jul 2017 19:41
PMCID: PMC5481186
Related URLs:
URI: https://repository.cshl.edu/id/eprint/35052

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