# Mechanisms of translational control

> **NIH NIH R35** · UNIVERSITY OF MICHIGAN AT ANN ARBOR · 2020 · $379,597

## Abstract

Project summary
 Despite being one of the most central processes in biology many key questions remain about how protein
translation by the ribosome is regulated. Translational control is fundamentally important for human health as
dysregulation of translation is known to be involved in myriad of diseases, including numerous cancers. Our
understanding of the translational control of gene expression is currently undergoing a paradigm switch. Until
recently it was thought that all translational control takes place when the ribosomes decide to, or not to, initiate
on a start codon. However, a wealth of recent data suggests that translation is also widely regulated after initiation
has occurred, during the subsequent `elongation' phase of translation. Thus, the regulation of translation
elongation is an expanding frontier for exploring the translational control of gene expression.
 My lab uses a powerful compliment of kinetic and genome-wide tools to investigate how the speed of
ribosome elongation can be modulated to regulate gene expression. We also directly collaborate with experts to
investigate both ribosome and mRNA structures. This proposal focuses on using these approaches investigate
situations at the molecular level where the slow progression of the ribosome has been linked to cell health and
viability, but where molecular mechanisms are unknown. Specifically, our work seeks to discover: 1) how nascent
peptides modulate the rate of translation, 2) how non-canonical movements of the ribosome change gene
expression, 3) how mRNA modifications impact translation rates, and 4) how post-translational modifications
impact the translation machinery. These studies will provide a biochemical framework for understanding how
controlling ribosome elongation rates contributes globally to gene expression.
 In summary, we fill crucial gaps in the burgeoning field of translation regulation via ribosome stalling
mechanisms. Our studies will reveal the breadth of gene regulation via translational stalling, and dissect the
molecular mechanism(s) of translational control. Overall, this work will challenge the long-held paradigm that the
ribosome indiscriminately translates the majority of sequences at a mostly uniform rate. In the long-term, our
findings could be key for the development of targeted therapeutics to treat diseases linked to alterations of
translation elongation.

## Key facts

- **NIH application ID:** 9996723
- **Project number:** 5R35GM128836-03
- **Recipient organization:** UNIVERSITY OF MICHIGAN AT ANN ARBOR
- **Principal Investigator:** Kristin S Koutmou
- **Activity code:** R35 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $379,597
- **Award type:** 5
- **Project period:** 2018-08-01 → 2023-07-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9996723

## Citation

> US National Institutes of Health, RePORTER application 9996723, Mechanisms of translational control (5R35GM128836-03). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/9996723. Licensed CC0.

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