# Sexual dimorphism of piRNA transcription and target silencing mechanisms in C. elegans

> **NIH NIH R01** · JOHNS HOPKINS UNIVERSITY · 2022 · $470,108

## Abstract

Abstract
The Piwi-interacting RNA (piRNA) pathway promotes animal fertility by protecting the germline genome against
mobile DNA elements. Despite this well-established paradigm, several critical gaps remain in our understanding
of piRNA mechanisms, including the sexual dimorphism of their biogenesis and downstream gene regulatory
functions. We discovered that the ancient SNAPc (or SNPC) transcription complex that transcribes small nuclear
RNAs (snRNAs) of the spliceosome has diversified in C. elegans to drive the expression of male- and female-
specific piRNAs, in addition to its canonical function in snRNA transcription. In the fly and human, the SNPC
holocomplex is composed of SNPC-1, SNPC-3, and SNPC-4 subunits, each encoded by a single gene. In
contrast, C. elegans expresses several paralogs of SNPC-1 and SNPC-3 that we propose dictate the specificity
of three distinct SNPC complexes. In particular, based on our published and preliminary data, we hypothesize
that the SNPC-1 paralogs comprise the primary specificity factors that define the unique functions of each SNPC
complex for either snRNA or sex-specific piRNA transcription. In this proposal, we will first investigate how this
specificity is achieved by identifying the cis-regulatory elements recognized by each SNPC transcription complex
(Aim 1). We will also determine the specificity domains, cofactors, and subcellular assembly of the piRNA and
snRNA SNPC complexes (Aim 2). Finally, we will characterize the biological phenotypes of the male and female
piRNA mutants and leverage these insights to predict and validate endogenous gene targets of sex-specific
piRNAs. Collectively, this research will bridge the gaps in our understanding of sexual dimorphism in piRNA
transcription and gene targeting mechanisms that ensure proper germline development and robust reproductive
capacity of animals.
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## Key facts

- **NIH application ID:** 10512577
- **Project number:** 1R01HD109667-01
- **Recipient organization:** JOHNS HOPKINS UNIVERSITY
- **Principal Investigator:** John Kim
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $470,108
- **Award type:** 1
- **Project period:** 2022-08-01 → 2027-04-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10512577

## Citation

> US National Institutes of Health, RePORTER application 10512577, Sexual dimorphism of piRNA transcription and target silencing mechanisms in C. elegans (1R01HD109667-01). Retrieved via AI Analytics 2026-05-25 from https://api.ai-analytics.org/grant/nih/10512577. Licensed CC0.

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