# RNA cytosine methylation in the rodent prefrontal cortex

> **NIH NIH F32** · ICAHN SCHOOL OF MEDICINE AT MOUNT SINAI · 2020 · $67,446

## Abstract

Project Summary and Abstract
!
The RNA methylome, in contrast to the DNA methylome, has barely been explored in the context of normal
and diseased brain development and function. RNA cytosine methylation (m5C), characterized by the addition
of a methyl group on the 5' position of a cytosine in RNA, is a novel modification only recently characterized in
mammalian tissue and most abundant in tRNAs. NSUN2, a tRNA methyltransferase that methylates the
variable loop of tRNA, is expressed at high levels in the central nervous system and has been linked to
neurodevelopmental defects in humans and mice. Humans with a mutation in the NSUN2 gene exhibit
intellectual disability accompanied by other neurological abnormalities, including microcephaly, speech delays,
and other cognitive impairments. Likewise, adult NSUN2 knockout mice exhibit deficits in cognitive and
emotional behavior, a phenotype which may be related to altered methylation at distinct tRNA cytosines during
embryonic stages of brain development leading to impaired neuronal survival and synaptic puncta in the
cortex. However, it is still unknown whether tRNA methylation patterns regulate brain function or behavioral
outcomes outside the realm of development. In the current proposal, I will focus on the regulation of RNA
cytosine methylation in the mouse brain and its role in cognitive behavior. In Aim 1 we will use viral
overexpression and knockdown of NSUN2 in the adult mouse PFC to elucidate the effect of altered NSUN2
expression on tRNA methylation in the PFC. Aim 2 will investigate cognitive and anxiety-like behaviors of
NSUN2-overexpressing and knockdown mice. Aim 3 will identify the downstream molecular consequences of
tRNA methylation on the accumulation of tRNA fragments and presence of stress granules and processing
bodies. The proposed research is significant because RNA cytosine methylation has still not been explored in
the adult brain, and understanding the role of tRNA methylation in the adult brain may elucidate mechanisms
underlying aberrant brain function during adulthood.

## Key facts

- **NIH application ID:** 9878931
- **Project number:** 5F32MH115565-03
- **Recipient organization:** ICAHN SCHOOL OF MEDICINE AT MOUNT SINAI
- **Principal Investigator:** Jennifer Blaze
- **Activity code:** F32 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $67,446
- **Award type:** 5
- **Project period:** 2018-03-01 → 2021-02-28

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9878931

## Citation

> US National Institutes of Health, RePORTER application 9878931, RNA cytosine methylation in the rodent prefrontal cortex (5F32MH115565-03). Retrieved via AI Analytics 2026-05-25 from https://api.ai-analytics.org/grant/nih/9878931. Licensed CC0.

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