# Mechanisms of Translation Initiation Mediated by mRNA Structure

> **NIH NIH R01** · UNIVERSITY OF ROCHESTER · 2021 · $327,316

## Abstract

Mechanisms of Translation Initiation Mediated by mRNA Structure
The Central Dogma of molecular biology is that DNA is used to make mRNA, which is used to make proteins.
The initiation of translation, the act of making proteins from messenger RNA (mRNA), is central to the
regulation of this process. Dysregulation of translation initiation plays an important role in a number of human
diseases including cancer. In eukaryotes including humans, the initiation of translation involves the recruitment
of factors that interact with the two (5' and 3') ends of the mRNA to make, in essence, a circle that is poised to
be translated. The recruitment of factors and the function of subsequent circularization are poorly understood.
We aim to take a novel look at this biological problem through the lens of physical chemistry of nucleic acids
and structural biology. Although factor-mediated circularization of mRNA is thought to be critical for protein
synthesis, this proposal puts forward an alternative hypothesis: formation of basepairing interactions within the
mRNA itself results in the circularization of the mRNA in the absence of the protein complexes. Hence, the
ends of the mRNA are inherently located close to one another. Such “circularization” could facilitate the
recruitment of the protein complexes and thereby aid translation initiation. To test our hypothesis, we will
experimentally examine whether the ends of mRNAs are in close proximity in the absence of protein initiation
complexes. We will also test whether the disruption of basepairing interactions between mRNA ends inhibits
protein synthesis and binding of translation initiation factors to the mRNA. The proposed studies will span a
spectrum of approaches including single-molecule fluorescent microscopy and fluorescent spectroscopy,
chemical probing of RNA structure, computational biology and examination of translation in vivo. Our proposed
studies will elucidate whether mRNA secondary structure and end-to-end distance are major determinants that
govern translational initiation in eukaryotes.

## Key facts

- **NIH application ID:** 10155506
- **Project number:** 5R01GM132041-03
- **Recipient organization:** UNIVERSITY OF ROCHESTER
- **Principal Investigator:** Dmitri Ermolenko
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $327,316
- **Award type:** 5
- **Project period:** 2019-05-01 → 2023-04-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10155506

## Citation

> US National Institutes of Health, RePORTER application 10155506, Mechanisms of Translation Initiation Mediated by mRNA Structure (5R01GM132041-03). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10155506. Licensed CC0.

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