# Expanding the biological roles of N-terminal methylation

> **NIH NIH R35** · STATE UNIVERSITY OF NEW YORK AT BUFFALO · 2024 · $13,815

## Abstract

Project Summary:
Post-translational modification of N-terminal α-amino groups is a highly conserved and vastly utilized process
seen in all species from bacteria to mammals. Dr. Schaner Tooley pioneered the field of N-terminal
methylation by identifying the first two eukaryotic N-terminal methyltransferases, NRMT1 and NRMT2. She
went on to characterize the consensus sequence of these enzymes, identify dozens of their substrates, and
show N-terminal methylation regulates protein/DNA interactions. Her lab was also the first to show that, like
histone PTMs, Nα-PTMs are part of a functional code. They identified the first protein known to exist in both
Nα-acetyl and Nα-methyl forms, Myosin Light Chain 9 (MYL9). They demonstrated that these two Nα-PTMs
create distinct proteoforms of MYL9, with unique protein binding partners, internal PTM patterns, and cell
compartment-specific functions. They have also demonstrated important roles for NRMT1 in oncogenesis
and aging. NRMT1 loss in breast cancer cells promotes proliferation, migration, colony formation, and
xenograph growth. NRMT1 knockout in mice promotes phenotypes associated with premature aging,
including early graying, kyphosis, and dermal fibrosis. They now want to expand understanding of the
biochemistry of NRMT1 regulation, identify additional substrates regulated by the Nα-PTM code, and
mechanistically characterize a newly discovered role for NRMT1 in stem cell fate determination. Successful
completion of these goals will provide a more global understanding of NRMT1 function and help better
develop NRMT1 as a therapeutic for human cancers and age-related disorders.

## Key facts

- **NIH application ID:** 11098902
- **Project number:** 3R35GM144111-03S2
- **Recipient organization:** STATE UNIVERSITY OF NEW YORK AT BUFFALO
- **Principal Investigator:** Christine E Schaner-Tooley
- **Activity code:** R35 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $13,815
- **Award type:** 3
- **Project period:** 2022-01-01 → 2026-12-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/11098902

## Citation

> US National Institutes of Health, RePORTER application 11098902, Expanding the biological roles of N-terminal methylation (3R35GM144111-03S2). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/11098902. Licensed CC0.

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