# Translational control by 5'-UTR elements

> **NIH NIH R00** · UNIVERSITY OF MICHIGAN AT ANN ARBOR · 2024 · $10,530

## Abstract

Aberrant protein synthesis is associated with a variety of disease states such as cancer and
neurodegeneration. The protein output per mRNA is strongly affected by a combination of cis elements and
trans factors that together control the rate of recruitment of ribosomes to the 5′-untranslated region (5′-UTR).
Different 5′-UTRs are sufficient to confer a thousand-fold range of translation output both in vivo and in vitro,
but the mechanisms underlying these large effects are unknown in most cases. This R00 Pathway to
Independence Award seeks to understand the 5′-UTR regulatory code controlling mRNA translation by
answering two fundamental questions: (1) what are the components of the code? And (2) what is the
mechanism by which the components affect translational activity? To answer these questions Dr. Niederer will
take advantage of a cellular condition where widespread changes in 5′-UTR usage have been observed-
cancer. During the K99 phase, Dr. Niederer Used a novel technical approach to directly measure ribosome
recruitment levels to thousands of differentially expressed 5′-UTR sequences (previous Aim 1). While the
changes in 5′-UTR usage are well known, their effect on ribosome recruitment is more or less completely
unknown. In this R00 phase, Dr. Niederer will use a combination of biochemical and genetic studies to identify
the readers of these functional RNA elements (new Aim 1). This work will be extended by the efforts of Cesar
Martinez, who will be performing mutagenesis to delineate the functional boundaries of the identified elements.
This will be critical for identifying candidate readers that are specific to the newly identified translational
repressors and enhancers. Dr. Niederer will then characterize the candidate readers and determine their role in
supporting translational reprogramming in cells exposed to oncogenic insults or undergoing stress response.
Additional work will measure ribosome recruitment to additional 5′-UTRs of interest, including those (1)
containing pathogenic SNPs and (2) exhibiting tissue specific expression (new Aim 2). The results of this work
are likely to reveal novel mechanisms of translation regulation, which will not only further our understanding of
a fundamental cellular process but will also have implications for human health and disease.

## Key facts

- **NIH application ID:** 10984186
- **Project number:** 3R00GM135533-04S1
- **Recipient organization:** UNIVERSITY OF MICHIGAN AT ANN ARBOR
- **Principal Investigator:** Rachel O. Niederer
- **Activity code:** R00 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $10,530
- **Award type:** 3
- **Project period:** 2020-09-01 → 2026-01-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10984186

## Citation

> US National Institutes of Health, RePORTER application 10984186, Translational control by 5'-UTR elements (3R00GM135533-04S1). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10984186. Licensed CC0.

---

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