# The mechanisms of mRNA recruitment to the human ribosome

> **NIH NIH R35** · UNIVERSITY OF CALIFORNIA AT DAVIS · 2024 · $401,250

## Abstract

PROJECT SUMMARY
Changes in physiological stimuli reprogram the translation machinery to alter preferential recruitment of
mRNAs to the ribosome and which start site on a mRNA is selected. Genome wide analysis using
ribosome profiling has revealed far more extensive regulation of these events than previously appreciated,
yet the mechanism of mRNA recruitment and its regulation remains poorly understood. This knowledge
gap persists mainly because of difficulties in determining which intermediate step(s) in the initiation
pathway function as kinetic checkpoints to control mRNA recruitment. To date, initiation pathway
intermediates have largely been identified on the basis of their thermodynamic stability which must
withstand traditional assays (e.g. sucrose gradients and immunoprecipitations). These approaches take
minutes to hours to perform, and/or require cross-linking agents to stabilize them, but most intermediates
prior to initiation codon selection occur on the sub-second to second time scale. To determine how
mRNAs are selected for translation, one must develop and use assays that can precisely monitor the
formation of pathway intermediates in real-time. To overcome this bottleneck and move the field forward,
we have developed innovative ensemble and single-molecule fluorescence-based assays that can
monitor the rate of mRNA recruitment to the ribosome in real-time. Our highly purified reconstituted
system will enable us to successfully test and build models with which to understand mRNA recruitment
and its regulation. Models that we generate will be tested using translation assays in cell-free extracts and
intact cells. Our long-term objective is to understand the mechanism by which alterations in initiation factor
availability and their post-translational modification reprograms the translational apparatus to control
which mRNAs are translated in response to physiological stimuli.

## Key facts

- **NIH application ID:** 10764630
- **Project number:** 1R35GM152137-01
- **Recipient organization:** UNIVERSITY OF CALIFORNIA AT DAVIS
- **Principal Investigator:** Christopher S Fraser
- **Activity code:** R35 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $401,250
- **Award type:** 1
- **Project period:** 2024-01-01 → 2028-12-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10764630

## Citation

> US National Institutes of Health, RePORTER application 10764630, The mechanisms of mRNA recruitment to the human ribosome (1R35GM152137-01). Retrieved via AI Analytics 2026-05-25 from https://api.ai-analytics.org/grant/nih/10764630. Licensed CC0.

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