# Deciphering the phosphorylation pattern of RNA polymerase II for eukaryotic transcription

> **NIH NIH R35** · UNIVERSITY OF TEXAS AT AUSTIN · 2024 · $597,526

## Abstract

ABSTRACT
The C-terminal domain (CTD) of the largest RNA polymerase II subunit is a unique CTD sequence
(Y1S2P3T4S5P6S7) repeated many times and is mostly conserved in eukaryotes. This domain coordinates the
recruitment of transcriptional factors to Pol II through its post-translational modifications, the loss of which
cripples the highly efficient transcription process and causes the cell to die. The accurate phosphorylation state
of different residues in the CTD heptad repeats by kinase and phosphatases is crucial to precisely recruiting
proteins to mediate the transcription process. Our lab utilizes our extensive experience in protein chemistry to
understand the precise pattern of phosphorylation during transcription by investigating the activity and specificity
of these kinases and phosphatases. We seek to understand how the post-translational modifications of CTD are
altered during biological events and how such changes are reflected in the outcome of transcription. We use
multi-disciplinary methods including structural biology, biochemistry, mass spectrometry methodology, and
global transcriptome analysis to investigate the molecular mechanism of how different modification states of RNA
polymerase II coordinate the eukaryotic transcription.
Equipped with extensive knowledge about the phosphatase function and activity, we further explore how the
chemical inhibition of SCP1, a human phosphatase belonging to HAD superfamily, thwarts some of the growth
glioblastoma cells. We utilized our experience in structural-based inhibitor design to identify covalent and non-
covalent inhibitors targeting this unique phosphatase.

## Key facts

- **NIH application ID:** 10778554
- **Project number:** 5R35GM148356-02
- **Recipient organization:** UNIVERSITY OF TEXAS AT AUSTIN
- **Principal Investigator:** Yan Jessie Zhang
- **Activity code:** R35 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $597,526
- **Award type:** 5
- **Project period:** 2023-02-06 → 2028-01-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10778554

## Citation

> US National Institutes of Health, RePORTER application 10778554, Deciphering the phosphorylation pattern of RNA polymerase II for eukaryotic transcription (5R35GM148356-02). Retrieved via AI Analytics 2026-06-12 from https://api.ai-analytics.org/grant/nih/10778554. Licensed CC0.

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