# Regulation of mRNA translation by cis-acting sequences and trans-acting factors

> **NIH NIH R35** · CARNEGIE-MELLON UNIVERSITY · 2024 · $365,148

## Abstract

While the regulation of gene expression is well recognized as being important to human
disease, there is a fundamental gap in understanding the role of post-transcriptional
processes. Because post-transcriptional processes are critical for the regulation of
protein production, addressing this knowledge gap will facilitate better models of the
relationship between genotype and phenotype. Like transcription, mRNA translation is
regulated by cis-acting sequences and trans-acting factors. upstream Open Reading
Frames (uORFs) are cis-acting regulatory element found in most human genes, and
some disease-linked mutations appear to alter the presence of uORFs. The primary
focus of my laboratory is to determine how cis-acting sequences and trans-acting factors
control translation. Our goal for the next funding period is to determine the functions of
human uORFs and evaluate their regulation by trans-acting RNA binding proteins
(RBPs). To accomplish this, we have adapted our yeast Massively Parallel Reporter
Assays (MPRAs) for use in human tissue culture. In addition, our computational analysis
has identified thousands of primate-conserved human uORFs, many of which have
conserved RBP binding sites downstream of their start codons. The vast majority of
these uORFs have not been functionally studied. Our innovative approach combines
exquisite systems biology tools with cutting-edge computational modeling to investigate
the functions of these ubiquitous cis-regulatory elements. The proposed research is
significant because it is expected to fundamentally advance our understanding of human
gene regulation.

## Key facts

- **NIH application ID:** 10830290
- **Project number:** 5R35GM145317-03
- **Recipient organization:** CARNEGIE-MELLON UNIVERSITY
- **Principal Investigator:** Charles Joel McManus
- **Activity code:** R35 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $365,148
- **Award type:** 5
- **Project period:** 2022-05-01 → 2027-04-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10830290

## Citation

> US National Institutes of Health, RePORTER application 10830290, Regulation of mRNA translation by cis-acting sequences and trans-acting factors (5R35GM145317-03). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10830290. Licensed CC0.

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