# Tudor Domain Proteins in Germline Genome Defense

> **NIH NIH R01** · MICHIGAN STATE UNIVERSITY · 2022 · $322,787

## Abstract

PROJECT SUMMARY
Transposable elements (TEs) are “genomic parasites” that can replicate and re-integrate
into the host cell genome. Uncontrolled TE activity in germ cells leads to DNA damage,
disruption of gametogenesis, and infertility. In mammalian male germ cells, the PIWI-
piRNA pathway uses small RNAs as a guide to silence mobile TEs to protect genome
integrity and sustain fertility. The proper production of piRNAs is critical for TE silencing
and spermatogenesis. However, the mechanisms governing piRNA biogenesis are not
well understood. In particular, the roles of many RNA binding proteins during piRNA
biogenesis remain elusive. By studying a subgroup of Tudor domain proteins that also
harbor LOTUS domains, we discovered that TDRD5 is a novel RNA binding protein
critical for piRNA biogenesis in mice. Strikingly, we have discovered a novel RNA
binding property of LOTUS domains that is conserved in bacteria, plants and animals.
This binding property is different from reported protein binding feature of some animal
LOTUS domains. We hypothesize that animal LOTUS domains have both RNA and
protein binding activities and that the LOTUS group of Tudor domain proteins together
play critical roles in mammalian piRNA biogenesis. To test this hypothesis, we will use
biochemical approaches and mouse models to: 1) Clarify the RNA and protein binding
activities of the LOTUS domain superfamily; 2) Determine the mechanism of a specific
LOTUS domain-RNA interaction; and 3) Define the functional involvement of LOTUS
domain proteins in piRNA biogenesis and Vasa regulation in mice. These studies will
provide valuable new insights into the mechanisms of piRNA biogenesis that safeguard
germline genome integrity to sustain male fertility and expand our knowledge in broader
RNA biology and developmental biology.

## Key facts

- **NIH application ID:** 10394251
- **Project number:** 5R01HD084494-08
- **Recipient organization:** MICHIGAN STATE UNIVERSITY
- **Principal Investigator:** Chen Chen
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $322,787
- **Award type:** 5
- **Project period:** 2015-09-01 → 2024-04-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10394251

## Citation

> US National Institutes of Health, RePORTER application 10394251, Tudor Domain Proteins in Germline Genome Defense (5R01HD084494-08). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/10394251. Licensed CC0.

---

*[NIH grants dataset](/datasets/nih-grants) · CC0 1.0*