# Mitochondria-anchored protein complexes in piRNA biogenesis and function

> **NIH NIH R01** · MICHIGAN STATE UNIVERSITY · 2020 · $308,195

## Abstract

PROJECT SUMMARY
Pachytene piRNAs are a population of small regulatory RNAs unique to mammals that
regulates spermatogenesis and fertility. In mice, pachytene piRNAs are generated from
long piRNA precursors through cleavage by the piRNA processing machinery and
loaded onto two cytoplasmic PIWI proteins MIWI and MILI. However, the mechanism by
which PIWI proteins are recruited to piRNA processing machinery to participate in piRNA
biogenesis remains elusive. Here we provide preliminary data that reveal a novel genetic
separation of MIWI and MILI to differentially enter into the piRNA processing machinery.
This segregation is mediated by a mitochondria-anchored protein complex that
specifically interacts with MIWI but not MILI. We hypothesize that distinct mitochondria-
anchored complexes differentially direct different PIWI proteins into the piRNA pathway
during pachytene piRNA processing. To test this hypothesis, we will use biochemical
and mouse genetic approaches to: 1) understand the functional importance of specific
mitochondria-based protein interactions in directing piRNA biogenesis and germ cell
function; 2) define the coupling mechanism for PIWI protein recruitment and downstream
piRNA processing; 3) explore a specific MILI recruiting mechanism to enter into the
piRNA pathway. These studies will provide novel insight into the organizing principle of
the piRNA processing machinery and the understanding of mechanism underlying
pachytene piRNA biogenesis and its relevance to normal spermatogenesis and fertility.

## Key facts

- **NIH application ID:** 9999625
- **Project number:** 5R01GM132490-02
- **Recipient organization:** MICHIGAN STATE UNIVERSITY
- **Principal Investigator:** Chen Chen
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $308,195
- **Award type:** 5
- **Project period:** 2019-09-01 → 2023-05-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9999625

## Citation

> US National Institutes of Health, RePORTER application 9999625, Mitochondria-anchored protein complexes in piRNA biogenesis and function (5R01GM132490-02). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/9999625. Licensed CC0.

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