# Determinants and consequences of translation elongation rate

> **NIH NIH R01** · UNIVERSITY OF CALIFORNIA BERKELEY · 2020 · $320,220

## Abstract

Project summary
We propose to use quantitative, high-throughput methods to understand the consequences of variation in
translation elongation on gene expression. New methods including ribosome proﬁling provide a genome-wide
view of the motion of ribosomes along transcripts. We recently developed a neural network based on ribosome
proﬁling data that captures information about what makes a ribosome move faster or slower, and then used
that same information to design synonymous sequences that are not just decoded at different rates but also
actually make more or less protein. This raises two questions that we propose to address here: how does slow
decoding result in diminished protein expression, and what consequences does this rate variation have in vivo?
First, we will expand our preliminary results from yeast, adapting our neural network model to understand
the impact of variation in translation elongation in mammalian systems. We will measure changes in
translation elongation in different cell types and with differential activity of translation elongation factors.
Second, we will investigate and model the interplay between translation initiation and translation elongation
rate to understand how translation elongation can be rate-limiting for protein production. We will also identify
trans-acting factors that modulate this effect, using a genome wide CRISPR screen. Third, we will develop a
more complete neural network model relating gene sequence to ultimate translation output, incorporating not
just local sequence context but also positional effects and other factors. This proposal presents new
experimental systems that can quickly and sensitively measure the consequences of codon choice and identify
factors affecting how different codons determine translation output.

## Key facts

- **NIH application ID:** 9898394
- **Project number:** 5R01GM132104-02
- **Recipient organization:** UNIVERSITY OF CALIFORNIA BERKELEY
- **Principal Investigator:** Liana Faye Lareau
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $320,220
- **Award type:** 5
- **Project period:** 2019-04-01 → 2024-03-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9898394

## Citation

> US National Institutes of Health, RePORTER application 9898394, Determinants and consequences of translation elongation rate (5R01GM132104-02). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/9898394. Licensed CC0.

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