# Function of PIW1/Argonuate Proteins in Spermatogenesis

> **NIH NIH R01** · YALE UNIVERSITY · 2022 · $418,991

## Abstract

One of the most exciting advances in biomedical research is the discovery of small RNAmediated
gene regulation mechanisms. Our research supported by this R01 since 2002 has
contributed significantly to this advancement: In the previous funding period, we discovered and
characterized the function of mammalian Piwi/Argonaute proteins that are central to small RNA
mechanisms. In the beginning of the current funding period, we further discovered that Piwi
proteins bind to a complex class of more than 60,000 small non-coding RNAs that we called
PIWI-interacting RNAs (piRNAs). Most piRNAs are encoded by intergenic “junk” DNA that is
mostly heterochromatin. The discovery of piRNAs reveals a new and surprisingly complex
dimension of biology, and was voted by the Science magazine as one of the ten Breakthroughs
of 2006. Remarkably, Piwi proteins and piRNAs are abundantly expressed only in
spermatogenic cells. We and others have shown that Piwi proteins play key roles in
spermatogenesis in Drosophila, C. elegans, zebrafish, and mice. We have also shown that the
overexpression of the human piwi gene (hiwi) is highly correlated to seminomas. To explore the
mechanisms underlying the spermatogenic functions of Piwi proteins, we have recently
demonstrated in Drosophila that Piwi proteins regulate the epigenetic state and transposon
activity and in mice that MILI also binds to chromatin. Despite this exciting progress, the function
of piRNAs has not been directly demonstrated in any system. The goal of this proposal is to
demonstrate the function of piRNAs during spermatogenesis. Our working hypothesis is that
piRNAs guide nuclear PIWI proteins to specific genomic loci for epigenetic regulation, which, in
the case of transposons, lead to their silencing. To test this hypothesis and to explore the
function of piRNAs, we propose to: (1) Determine the biological function of piRNA clusters
during spermatogenesis. (2) Investigate the epigenetic effect of specific piRNAs to the genome.
(3) Determine whether piRNAs are required for PIWI-targeting to genomic sequences. (4)
Determine whether piRNAs are required for suppressing transposition.

## Key facts

- **NIH application ID:** 10321306
- **Project number:** 5R01HD042012-20
- **Recipient organization:** YALE UNIVERSITY
- **Principal Investigator:** HONGYING QI
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $418,991
- **Award type:** 5
- **Project period:** 2002-04-01 → 2023-12-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10321306

## Citation

> US National Institutes of Health, RePORTER application 10321306, Function of PIW1/Argonuate Proteins in Spermatogenesis (5R01HD042012-20). Retrieved via AI Analytics 2026-06-10 from https://api.ai-analytics.org/grant/nih/10321306. Licensed CC0.

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