# Post-transcriptional mRNA regulation in the mammalian nervous system

> **NIH NIH R35** · YALE UNIVERSITY · 2024 · $494,400

## Abstract

The overall goal of research in my lab is to deepen our understanding of the roles of post-transcriptional gene
regulation in the mammalian nervous system and how its dysregulation underlies human disease. In the next
five years, we will build upon our previous work on neuronal mRNA metabolism and translation control and
focus on three interconnected areas: 1} The impact of microsatellite repeat expansion on mRNA processing
and translation. We will conduct targeted and genome-wide analyses to systematically identify the cis-elements
and trans-factors that modulate noncanonical processing and translation of repeat-containing RNAs. 2} The
functions and regulation of alternative translation initiation. Through our in-depth investigation of a conserved
bi-functional mRNA that encodes two proteoforms of the neuronal pentraxin receptor (NPR}, we hope to
uncover general principles that will inform our understanding of the regulatory impact of alternative start codon
usage. 3} Quantitative measurement of mRNA translation efficiency (TE}. While ribosome footprint profiling, or
Ribo-seq, is widely used to measure TE at a transcriptome scale, our recent findings suggest that conventional
Ribo-seq procedures may not accurately capture the magnitude of TE regulation. By comparing Ribo-seq to
directly measure TE data and optimizing Ribo-seq procedures, we will reexamine fundamental questions about
translation control in mammalian cells. Results from these analyses may challenge existing dogmas and open
up new lines of investigations.

## Key facts

- **NIH application ID:** 10765053
- **Project number:** 1R35GM152208-01
- **Recipient organization:** YALE UNIVERSITY
- **Principal Investigator:** Junjie Guo
- **Activity code:** R35 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $494,400
- **Award type:** 1
- **Project period:** 2023-12-15 → 2028-11-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10765053

## Citation

> US National Institutes of Health, RePORTER application 10765053, Post-transcriptional mRNA regulation in the mammalian nervous system (1R35GM152208-01). Retrieved via AI Analytics 2026-05-27 from https://api.ai-analytics.org/grant/nih/10765053. Licensed CC0.

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