# The DF phospho-code regulating the degradation of m6A mRNA

> **NIH NIH K22** · COLUMBIA UNIVERSITY HEALTH SCIENCES · 2024 · $192,456

## Abstract

PROJECT SUMMARY:
N6-methyladenosine (m6A), the most abundant nucleotide modification in the transcriptome, has the well-
established function of causing instability of modified mRNAs. Importantly, differentiation of hematopoietic stem
cells is one of the most-well studied scenarios in which m6A-modified mRNAs appears to be preferentially
degraded. Although this degradation process appears to be a highly regulated event to ensure cellular
commitment, a clear mechanism of how this event is regulated is missing.
My recent work demonstrated that the major mediators of m6A-mRNA degradation are the YTHDF (DF)
proteins. Thus, a major goal is to understand how these proteins are regulated to trigger m6A mRNA
degradation. My working hypothesis, which is supported by preliminary data, is the existence of a specific DF
phosphorylation-code regulating the DF ability to degrade m6A-mRNA. In this proposal, I will map this DF
phospho-code, identify the DF targeting kinases, and determine how DF phosphorylation affects the
differentiation of hematopoietic stem cells. Overall this proposal may reveal how DF phosphorylation controls
m6A mRNA stability and its fundamental role during the differentiation commitment of the hematopoietic stem
cells.

## Key facts

- **NIH application ID:** 10911133
- **Project number:** 5K22CA258954-03
- **Recipient organization:** COLUMBIA UNIVERSITY HEALTH SCIENCES
- **Principal Investigator:** Sara Zaccara
- **Activity code:** K22 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $192,456
- **Award type:** 5
- **Project period:** 2022-09-01 → 2025-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10911133

## Citation

> US National Institutes of Health, RePORTER application 10911133, The DF phospho-code regulating the degradation of m6A mRNA (5K22CA258954-03). Retrieved via AI Analytics 2026-05-27 from https://api.ai-analytics.org/grant/nih/10911133. Licensed CC0.

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