# A Unified Atlas of Dynamic tRNA Function

> **NIH NIH R01** · UNIVERSITY OF CALIFORNIA SANTA CRUZ · 2021 · $529,206

## Abstract

The broad objective of this project is to better understand function, regulation, and the varied transcripts
produced by each individual human tRNA gene. We propose to sequence full-length tRNA and tRNA-derived
small RNA transcripts across many different tissue types for both human and the preferred mammalian model,
mouse. These data will complement existing large-scale data sets focusing only on protein coding genes,
giving an integrated view of tRNAs in the context of all other genes. With this new data, we will be able to
better annotate and predict tRNA expression breadth across tissues, identify atypical tRNAs with potentially
novel function, and recognize potentially disease-contributing mutations in human tRNA genes. The tRNA
research field will also greatly benefit by being able to apply the revolutionary CRISPR/Cas9 gene targeting
technique to individual tRNA genes for study – an experimental resource which we propose to develop. Thus,
the aims of this grant are as follow:
(1) Creation of new tRNA gene predictive models leveraging existing functional data with new insights in
 tRNA gene variation and the importance of external genomic features.
(2) Train new predictive models with state-of-the-art tRNA transcriptome analyses, currently absent from
 the public databases. We will generate a comparative atlas of tRNA expression in samples from a
 broad range of healthy tissues from human and mouse, matching the tissue distribution of the NIH
 Genotype-Tissue Expression (GTEx) project to complement gene expression data for protein coding
genes.
(3) Integrate tRNA Atlas data with epigenomic and other published functional data within the Genomic
 tRNA Database. Using the framework of this database, we will establish robust functional ortholog
 maps between species, starting with human and mouse, to enable researchers to identify the best
 candidates for study of human genes in model organisms.
(4) Develop a library of human CRISPR/Cas9 guide RNAs to enable individual tRNA gene targeting and
 characterization. We will select a representative subset of fifteen tRNAs of special interest for study,
 based on functional predictions and expression data collected from Aims 1 and 2.
 These new data, integrated into the most widely used tRNA gene database, along with improved tools
for predicting and testing gene function, will enable and accelerate biomedical research in the tRNA community.
Our interdisciplinary research group is ideally suited to carry out these aims, as we have demonstrated
expertise in both computational analysis and development of molecular biology techniques enabling study of
tRNA biology.

## Key facts

- **NIH application ID:** 10112281
- **Project number:** 5R01HG006753-07
- **Recipient organization:** UNIVERSITY OF CALIFORNIA SANTA CRUZ
- **Principal Investigator:** Todd Michael Lowe
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $529,206
- **Award type:** 5
- **Project period:** 2012-07-16 → 2023-02-28

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10112281

## Citation

> US National Institutes of Health, RePORTER application 10112281, A Unified Atlas of Dynamic tRNA Function (5R01HG006753-07). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10112281. Licensed CC0.

---

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