# Sperm tsRNAs/rsRNAs and their RNA modifications in diet-induced epigenetic inheritance > **NIH NIH R01** · UTAH STATE HIGHER EDUCATION SYSTEM--UNIVERSITY OF UTAH · 2024 · $703,373 ## Abstract Project summary: Increasing lines of evidence in mammals have shown that certain acquired traits during paternal environmental exposure (e.g., unhealthy diet) can be “memorized” in sperm and transmitted to the future generations without altering the DNA sequence. Our research seeks to unravel the epigenetic mechanisms by which paternal environmental factors, like diet, are encoded in sperm RNA and influence offspring health. Building on our discovery of tRNA-derived small RNAs (tsRNAs) and rRNA-derived small RNAs (rsRNAs) in sperm and their role in intergenerational inheritance, we have raised the concept of 'sperm RNA code'—an RNA expression/modification signature—that is sensitive to paternal experiences such as diet and stress. However, the mechanisms by which sperm tsRNAs/rsRNAs and their modifications impact offspring by penetrating the embryo development process remain largely unknown and await to be addressed. This renewal of our NIH R01 project aims to advance the study of epigenetic inheritance via sperm RNAs, which will extend from our innovative tools developed from the last funding period, including PANDORA-seq, which uncovers modified tsRNA/rsRNA that are previously undetectable; and MLC-seq, a novel mass spectrometry-based method to map multiple RNA modifications of tsRNAs/rsRNAs. We’ll use these new tools to uncover the alterations of tsRNAs/rsRNAs and their RNA modification under high-fat diet (HFD), and how they regulate offspring phenotype via early embryonic events such as lineage differentiation. Our preliminary data reveal that tsRNAs and rsRNAs are uniquely expressed in sperm heads, and that some of them are regulators of cell lineage differentiation in mouse embryonic stem cells, leading to the hypothesis that they can skew the embryonic lineage balance between the inner-cell mass (ICM) and trophectoderm (TE), thus a mechanism for influencing balanced fetus-placenta development. We will systematically explore this potential mechanism by 1) leverage PANDORA- seq and MLC-seq to identify the modified sperm tsRNAs/rsRNAs responsive to HFD and to examine their roles by zygotic RNA injection regarding regulations on embryonic cell fate decisions and subsequent fetus:placenta development; 2) quantify the relationship between dysregulated fetus-placenta weight ratio during mid- and late- pregnancy to metabolic phenotypes in offspring in a sex-specific manner. 3) Investigate the molecular interplay of tsRNAs/rsRNAs with nuclear ribonucleoproteins, providing insights into how these interactions may regulate ribosomal function and translational specificity and thus, embryonic cell lineage outcomes. Collectively, this research strives to dissect the complex cellular mechanisms underpinning paternal environmental exposure- induced epigenetic inheritance. It aims to establish deeper insight in understanding the cellar and developmental origin of sperm RNA-induced epigenetic inheritance upon paternal environmental exposure. ## Key facts - **NIH application ID:** 10999750 - **Project number:** 2R01HD092431-06 - **Recipient organization:** UTAH STATE HIGHER EDUCATION SYSTEM--UNIVERSITY OF UTAH - **Principal Investigator:** Qi Chen - **Activity code:** R01 (R01, R21, SBIR, etc.) - **Funding institute:** NIH - **Fiscal year:** 2024 - **Award amount:** $703,373 - **Award type:** 2 - **Project period:** 2017-08-09 → 2029-05-31 ## Primary source NIH RePORTER: https://reporter.nih.gov/project-details/10999750 ## Citation > US National Institutes of Health, RePORTER application 10999750, Sperm tsRNAs/rsRNAs and their RNA modifications in diet-induced epigenetic inheritance (2R01HD092431-06). Retrieved via AI Analytics 2026-05-26 from https://api.ai-analytics.org/grant/nih/10999750. Licensed CC0. --- *[NIH grants dataset](/datasets/nih-grants) · CC0 1.0*