# 3' tsRNAs: biologic function and pre-clinical targeting for treating human disease

> **NIH NIH R01** · STANFORD UNIVERSITY · 2024 · $518,152

## Abstract

ABSTRACT
Over the last decade we characterized and studied the properties of various tRNA derived
small RNAs (tsRNAs). In recent years, we have focused on one class commonly referred
to as 3’tsRNAs (derived from the 3’end of mature tRNAs) because they are the least well
studied but appear to play a role in tissue regeneration (e.g., liver regeneration) and
hyperproliferative states including cancer. Here we plan to establish the potential of targeting
the 3’tsRNAs for therapeutic purposes. Recently, we established that one specific RNA, the
22nt CAG-Leucine 3’tsRNA, which when down regulated by the addition of antisense
oligonucleotides in rapidly dividing but not quiescent cells inhibit ribosome biogenesis. Loss
of this specific tsRNA limits the translation (at the elongation step) of at least one ribosomal
protein mRNA. This results in a block in rRNA processing and rapid cellular apoptosis. In
contrast, the addition of a 3’tsRNA mimic increases cellular proliferation and can complement
the ribosome biogenesis defect in cells. We propose to further identify other 3’tsRNA-mRNA
interactions and establish their biologic and molecular function and develop gene therapy
and oligonucleotide antisense delivery technologies to pursue the therapeutic potential of
manipulating 3’tsRNAs in animals. Although the tsRNAs are expressed in many tissues, we
will focus these studies on the liver including liver cancer. This work will provide new
information related to 3’tsRNA function in gene regulation and cellular homeostasis in health
and disease states, as well as establish their potential therapeutic value by the proposed
preclinical human xenotransplant murine animal models. In the amended application, we
removed all the studies related to screening for improved LNPs outlined in previous specific
aim 3 as suggested by the reviewers.

## Key facts

- **NIH application ID:** 10884932
- **Project number:** 5R01CA277059-02
- **Recipient organization:** STANFORD UNIVERSITY
- **Principal Investigator:** Mark A Kay
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $518,152
- **Award type:** 5
- **Project period:** 2023-07-08 → 2028-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10884932

## Citation

> US National Institutes of Health, RePORTER application 10884932, 3' tsRNAs: biologic function and pre-clinical targeting for treating human disease (5R01CA277059-02). Retrieved via AI Analytics 2026-05-25 from https://api.ai-analytics.org/grant/nih/10884932. Licensed CC0.

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