Project III. Understanding the architecture, regulation, and function of piRNA-producing genes Phillip D. Zamore, P.I. Project Summary In flies, mammals, and worms, PIWI-interacting RNAs (piRNAs) silence transposons and repetitive elements, protecting the germline genome from DNA damage and mutation and ensuring that genetic information passes faithfully from generation to generation. They also have other, poorly understood functions. We propose to define the gene structure, genomic architecture, and regulation of the piRNA-producing genes in mice, flies, and worms. We will then use this information to investigate why some long RNAs make piRNAs while others do not. We will also explore how full-length piRNA precursor transcripts, often tens of kilobases long, are converted into mature piRNAs just 23?35 nt long. Finally, we will test a variety of hypotheses, generated from our data, as to how piRNAs function, particularly in mammals, where most piRNAs do not correspond to transposons. To pursue these aims, we will combine genetics, high-throughput sequencing, and classical biochemistry. We believe that by investigating a common set of questions about the piRNA pathway in three model animals, the conserved and divergent features we discover will yield a deeper understanding of this ancient pathway than could be achieved by working on a single species alone. Relevance Small RNAs called ?piRNAs? protect animal sperm and egg precursor cells from damage from selfish genetic elements called transposons or ?jumping genes.? Without piRNAs, animals from worms to mammals are sterile, yet we do not understand how piRNAs are made, and for many piRNAs, what they regulate. We hope to obtain a more complete and deeper understanding of this amazing process.

Agency
National Institute of Health (NIH)
Institute
Eunice Kennedy Shriver National Institute of Child Health & Human Development (NICHD)
Type
Research Program Projects (P01)
Project #
5P01HD078253-03
Application #
9233751
Study Section
Special Emphasis Panel (ZHD1-DSR-L)
Project Start
Project End
Budget Start
2017-03-01
Budget End
2018-02-28
Support Year
3
Fiscal Year
2017
Total Cost
$268,159
Indirect Cost
$108,064
Name
University of Massachusetts Medical School Worcester
Department
Type
Domestic Higher Education
DUNS #
603847393
City
Worcester
State
MA
Country
United States
Zip Code
01655
Tang, Wen; Tu, Shikui; Lee, Heng-Chi et al. (2016) The RNase PARN-1 Trims piRNA 3' Ends to Promote Transcriptome Surveillance in C. elegans. Cell 164:974-84
Tsuji, Junko; Weng, Zhiping (2016) DNApi: A De Novo Adapter Prediction Algorithm for Small RNA Sequencing Data. PLoS One 11:e0164228
Tran, Helene; Almeida, Sandra; Moore, Jill et al. (2015) Differential Toxicity of Nuclear RNA Foci versus Dipeptide Repeat Proteins in a Drosophila Model of C9ORF72 FTD/ALS. Neuron 87:1207-14
Chou, Min-Te; Han, Bo W; Hsiao, Chiung-Po et al. (2015) Tailor: a computational framework for detecting non-templated tailing of small silencing RNAs. Nucleic Acids Res 43:e109
Wang, Wei; Han, Bo W; Tipping, Cindy et al. (2015) Slicing and Binding by Ago3 or Aub Trigger Piwi-Bound piRNA Production by Distinct Mechanisms. Mol Cell 59:819-30