# A Genetic Circuit Formed by Ribosomes

> **NIH NIH DP1** · CORNELL UNIVERSITY · 2021 · $1,091,134

## Abstract

PROJECT SUMMARY
Following transcription, mRNAs transmit the genetic information that dictates protein production. In eukaryotes,
transcription and translation occur at different timings and in distinct subcellular compartments. It is commonly
believed that these two fundamental processes are uncoupled and have little “cross-talk”. Recent evidence
suggests that translation of aberrant mRNAs leads to genetic compensation, a transcriptional response to
rapidly upregulate genes with similar functions. However, the molecular mechanisms by which cytoplasmic
translation communicates with nuclear transcription remain elusive. During the course of studying translational
control in response to amino acid starvation, we observed transcriptional upregulation of genes undergoing
stress-induced ribosome pausing. Relying on a newly developed sequencing method, Ezra-seq, we discovered
the existence of endogenous ribosome footprints. We hypothesize that these mRNA fragments serve as novel
chromatin modulators by influencing gene expression in a sequence-dependent manner. The goal of this
proposal is to characterize the genetic circuit coupling cytoplasmic translation and nuclear transcription. By
identifying and mapping chromatin-associated ribosome footprints, we will elucidate the novel type of RNA-
mediated epigenetic regulation of gene expression. We propose that the genetic circuit formed by ribosomes
contributes to genetic robustness and is a common mechanism for stress adaptation. We will also explore the
potential of designing artificial ribosome footprints to achieve controllable gene expression, revealing new
routes toward novel therapeutics. The conceptual establishment of ribosome-mediated genetic circuit is
transformative in our understanding of the central dogma in molecular biology and opens a new research
avenue towards genetic reprogramming.

## Key facts

- **NIH application ID:** 10246829
- **Project number:** 5DP1GM142101-02
- **Recipient organization:** CORNELL UNIVERSITY
- **Principal Investigator:** Shu-Bing Qian
- **Activity code:** DP1 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $1,091,134
- **Award type:** 5
- **Project period:** 2020-09-30 → 2025-07-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10246829

## Citation

> US National Institutes of Health, RePORTER application 10246829, A Genetic Circuit Formed by Ribosomes (5DP1GM142101-02). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/10246829. Licensed CC0.

---

*[NIH grants dataset](/datasets/nih-grants) · CC0 1.0*