The piRNA pathway has a conserved role in transposon silencing and genome maintenance during germline development. Adaptation to new genome pathogens by the Drosophila piRNA genome defense system appears to be driven by transposition into heterochromatic clusters, which produce the primary piRNAs that to initiate silencing. The HP1 homolog Rhino binds to clusters and is evolving rapidly under positive selection, suggesting that it may co-evolve with invading mobile elements. piRNA clusters and Rhino thus function at the adaptive interface between the piRNA pathway and transposons.
Aims1 and 2 combine evolutionary divergence and conservation with genetic, genomic, computational and cytological tools to define this critical interface. The ability to differentiate cluster transcripts from mRNAs is critical to the specificity of the piRNA dense system, and our recent data suggest that stalled spicing may mark cluster transcripts for processing into silencing RNAs.
Aim 3 focuses on the role of splicing in piRNA precursor sorting into the silencing pathway. These studies address mechanisms that maintain the inherited genome and are likely to directly impact reproductive health.

Public Health Relevance

Germline transmission of an unaltered genome is essential to species propagation. Transposons make up close to half of the human genome, and these mobile elements can induce mutations and represent a major treat to genome integrity. The piRNA pathway is an adaptive genome defense system that controls existing transposons and responds to new elements that invade the germline. The proposed studies address the basic mechanisms that allow this system to respond to invading genome pathogens, which is critical to reproductive health.

Agency
National Institute of Health (NIH)
Institute
Eunice Kennedy Shriver National Institute of Child Health & Human Development (NICHD)
Type
Research Project (R01)
Project #
5R01HD049116-14
Application #
9405328
Study Section
Development - 1 Study Section (DEV1)
Program Officer
Taymans, Susan
Project Start
2014-12-06
Project End
2019-11-30
Budget Start
2017-12-01
Budget End
2018-11-30
Support Year
14
Fiscal Year
2018
Total Cost
Indirect Cost
Name
University of Massachusetts Medical School Worcester
Department
Anatomy/Cell Biology
Type
Schools of Medicine
DUNS #
603847393
City
Worcester
State
MA
Country
United States
Zip Code
01655
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Zhang, Zhao; Wang, Jie; Schultz, Nadine et al. (2014) The HP1 homolog rhino anchors a nuclear complex that suppresses piRNA precursor splicing. Cell 157:1353-63
Zhuang, Jiali; Wang, Jie; Theurkauf, William et al. (2014) TEMP: a computational method for analyzing transposable element polymorphism in populations. Nucleic Acids Res 42:6826-38
Zhang, Zhao; Koppetsch, Birgit S; Wang, Jie et al. (2014) Antisense piRNA amplification, but not piRNA production or nuage assembly, requires the Tudor-domain protein Qin. EMBO J 33:536-9
Simkin, Alfred; Wong, Alex; Poh, Yu-Ping et al. (2013) Recurrent and recent selective sweeps in the piRNA pathway. Evolution 67:1081-90
Perrat, Paola N; DasGupta, Shamik; Wang, Jie et al. (2013) Transposition-driven genomic heterogeneity in the Drosophila brain. Science 340:91-5
Zhang, Fan; Wang, Jie; Xu, Jia et al. (2012) UAP56 couples piRNA clusters to the perinuclear transposon silencing machinery. Cell 151:871-84
Zhang, Zhao; Theurkauf, William E; Weng, Zhiping et al. (2012) Strand-specific libraries for high throughput RNA sequencing (RNA-Seq) prepared without poly(A) selection. Silence 3:9
Zhang, Zhao; Xu, Jia; Koppetsch, Birgit S et al. (2011) Heterotypic piRNA Ping-Pong requires qin, a protein with both E3 ligase and Tudor domains. Mol Cell 44:572-84
Khurana, Jaspreet S; Wang, Jie; Xu, Jia et al. (2011) Adaptation to P element transposon invasion in Drosophila melanogaster. Cell 147:1551-63

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