# New mechanisms and technologies for understanding post-transcriptional gene regulation in neurons

> **NIH NIH R35** · WEILL MEDICAL COLL OF CORNELL UNIV · 2021 · $1,084,800

## Abstract

The overall goal of our research program is to understand the intricate mechanisms by which neurons
establish the precise spatial and patterns of protein synthesis needed for synaptic plasticity and circuit
formation. Much of this regulation occurs at the RNA level, and my laboratory focuses on uncovering novel
regulatory mechanisms that enable this RNA-based control. Our research centers around three programs: (1)
Epitranscriptomic regulation of neuronal mRNAs. We are often credited with helping to start a new field of
RNA biology termed “epitranscriptomics,” the idea that mRNA fate and function is encoded in the RNA by
regulatory nucleotide modifications. A major program in my lab focuses on epitranscriptomic regulation of
mRNA fate in neurons by these modifications. (2) Deciphering the mechanism of RNA-directed epigenetic
silencing in fragile X syndrome. We recently showed that fragile X syndrome is a disease caused by CGG
repeat RNA. We found that this RNA forms a hybrid with complementary DNA to induce the epigenetic
silencing, which constitutes a new epigenetic pathway. We are committed to understanding this new area of
epigenetics and using knowledge of this pathway to develop a completely new approach to treat this major
neurological condition. (3) Technologies for revealing the function of the synaptic transcriptome. In
order to reveal new insights into RNA regulation in the brain, we develop novel technologies to enable imaging
and analysis of mRNA, perhaps most notably “RNA mimics of GFP,” including Spinach. We will take these
fluorogenic aptamers to the next level of brightness needed for the demanding imaging approaches used in live
functioning animals. Additionally, we will be developing new engineered aptamers that enable light-control of
synaptic mRNA translation. Overall, this research program will advance our understanding of post-
transcriptional gene regulation in neurons.

## Key facts

- **NIH application ID:** 10168672
- **Project number:** 5R35NS111631-03
- **Recipient organization:** WEILL MEDICAL COLL OF CORNELL UNIV
- **Principal Investigator:** SAMIE R JAFFREY
- **Activity code:** R35 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $1,084,800
- **Award type:** 5
- **Project period:** 2019-06-01 → 2027-05-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10168672

## Citation

> US National Institutes of Health, RePORTER application 10168672, New mechanisms and technologies for understanding post-transcriptional gene regulation in neurons (5R35NS111631-03). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10168672. Licensed CC0.

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