# Define piRNA biogenesis and function in mice

> **NIH NIH R35** · UNIVERSITY OF ROCHESTER · 2020 · $385,000

## Abstract

Reproduction is a fundamental feature of life. Animals usually require the differentiation of germ cells to create
gametes. The gametogenesis process is delicately regulated, defects in which lead to fertility problems that
impact 15% of humans. PIWI-interacting RNAs (piRNAs) are the most recently discovered and rapidly evolving
class of small RNAs in animals. In vertebrates, piRNAs are almost exclusively expressed in testis, and they are
essential for spermatogenesis. Some piRNAs guide PIWI proteins to silence transposable elements through
sequence complementarity; humans, mice, and rooster, however, also produce a distinct and abundant set of
non-repetitive piRNA sequences whose targets are unknown. My long-term goal is to understand the biology of
piRNAs and their functions in male fertility. There is no obvious conservation of piRNA species, and piRNAs
are heterogeneous: an organism carries millions of different piRNA sequences. The diversity is a result of their
unusual biogenesis. Long single-stranded piRNA precursors are cleaved into thousands of snippets, and these
fragments are loaded into PIWI proteins and become piRNAs. This fragmentation, which is poorly understood,
distinguishes piRNA processing from other RNA fates. My previous work defined the precise transcription units
of piRNA producing loci in mice, paving the way for the analysis of their post-transcriptional processing and
their functions. I have further developed new methodologies and animal models to overcome longstanding
roadblocks in piRNA research. In unpublished work, we found that ribosomes appear to participate in piRNA
biogenesis, and that piRNAs act to regulate sperm epigenomes including RNAs and histones. Here, I propose
to focus on two questions: 1) What principles designate a sequence to become a piRNA? 2) What is the
function of piRNAs beyond transposable element silencing in male reproduction? The findings from this work
may lead to the discovery of new mechanisms in male fertility and RNA biology.

## Key facts

- **NIH application ID:** 9980705
- **Project number:** 5R35GM128782-03
- **Recipient organization:** UNIVERSITY OF ROCHESTER
- **Principal Investigator:** Xin Li
- **Activity code:** R35 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $385,000
- **Award type:** 5
- **Project period:** 2018-08-01 → 2023-07-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9980705

## Citation

> US National Institutes of Health, RePORTER application 9980705, Define piRNA biogenesis and function in mice (5R35GM128782-03). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/9980705. Licensed CC0.

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