# Translational control by 5'-UTR elements

> **NIH NIH K99** · YALE UNIVERSITY · 2021 · $93,905

## Abstract

PROJECT SUMMARY/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 proposal for an NIH
K99/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. Using a novel technical approach Dr. Niederer will directly measure ribosome recruitment
levels to thousands of 5′-UTR sequences that are differentially expressed in cancer cells (Aim 1). While the
changes in 5′-UTR usage are well known, their affect on ribosome recruitment is more or less completely
unknown. Therefore, these studies can be used to identify functional RNA elements. Then, a combination of
biochemical and genetic studies will be used to identify the readers of these functional RNA elements (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. To complete these studies, Dr. Niederer will continue her training as a Postdoctoral Associate in
the Molecular Biophysics and Biochemistry department at Yale University. During the K99 phase Dr. Niederer
will receive invaluable training in computational methods to both identify functional RNA elements and
deconvolute their contributions to ribosome recruitment. Additionally, after working almost exclusively with the
model organism S. cerevisiae for over 10 years, she will expand her technical expertise to be able to conduct
experiments in the context of human cells. Using these skills, in the R00 phase, Dr. Niederer will characterize
the candidate readers and determine their role in supporting translational reprogramming. The Pathway to
Independence award will allow Dr. Niederer to gain the necessary technical expertise and professional skills to
become a competitive applicant for tenure track positions as a group leader.

## Key facts

- **NIH application ID:** 10242924
- **Project number:** 5K99GM135533-02
- **Recipient organization:** YALE UNIVERSITY
- **Principal Investigator:** Rachel O. Niederer
- **Activity code:** K99 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $93,905
- **Award type:** 5
- **Project period:** 2020-09-01 → 2022-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10242924

## Citation

> US National Institutes of Health, RePORTER application 10242924, Translational control by 5'-UTR elements (5K99GM135533-02). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10242924. Licensed CC0.

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