# Stability of a novel family of short noncoding RNAs, tRFs: Effect on oncogenesis

> **NIH NIH F30** · UNIVERSITY OF VIRGINIA · 2022 · $51,752

## Abstract

ABSTRACT
Cancer is a leading cause of morbidity and mortality in the United States. tRNA fragments (tRFs) have been
found to play a role in cancer pathogenesis. Our lab was one of the first to discover and characterize tRNA
fragments, a novel class of small non-coding RNAs, by systematically analyzing publicly available data.
Mechanistic insight into the function and regulation of tRFs is essential to understand their role in cancer, and
potentially identify pathways for novel therapeutics or patient stratification. We and others have shown that
tRFs can regulate gene expression at the post-transcriptional level. Despite some functional characterization of
tRFs, there is still a paucity of knowledge regarding tRF regulation. One way to gain insight into the regulation
of RNA is to measure RNA decay kinetics. Here, I propose to measure the decay rates of tRFs across species.
Elucidation of these parameters will give a better understanding of tRF stability, and will give insight into
regulation of tRF levels, a major question in the field. I will determine the regulation of tRF stability at a
mechanistic level. I will test whether tRF stability is regulated by various cis features, such as non-template
nucleotide additions and secondary structure, and trans features, mainly RNases. Preliminary data suggests
that DIS3, the RNase component of the nuclear RNA exosome, is important for regulating tRF levels.
Interestingly, DIS3 perturbations are thought to drive many cancers. Taken together, I hypothesize that tRF
stability is regulated by cis- and trans-factors, and that DIS3 is a key trans-factor that regulates tRF stability.
Finally, I hypothesize that DIS3 dysregulation in cancer promotes aberrant tRF expression, ultimately leading
to aberrant tRF-regulated target gene expression and changes in the oncogenic phenotypes of cancer cells. I
will pursue several opportunities, described in the proposal, to enhance my preclinical and clinical knowledge,
so that I can better integrate my research knowledge with my clinical interests. I will also pursue opportunities
to enhance my writing, networking and mentoring skills, so that I can eventually become a successful
independent PI as a physician-scientist.

## Key facts

- **NIH application ID:** 10443602
- **Project number:** 5F30CA254134-03
- **Recipient organization:** UNIVERSITY OF VIRGINIA
- **Principal Investigator:** Briana Wilson
- **Activity code:** F30 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $51,752
- **Award type:** 5
- **Project period:** 2020-07-01 → 2023-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10443602

## Citation

> US National Institutes of Health, RePORTER application 10443602, Stability of a novel family of short noncoding RNAs, tRFs: Effect on oncogenesis (5F30CA254134-03). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10443602. Licensed CC0.

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