# Elucidation of Integrator's Function

> **NIH NIH R01** · UNIVERSITY OF MIAMI SCHOOL OF MEDICINE · 2023 · $447,858

## Abstract

Project Summary
Integrator is a multi-protein complex stably associated with the C-terminal domain (CTD)
of RNA polymerase II (RNAPII). Integrator contains a catalytic RNA endonuclease
subunit (INTS11) with high degree of homology to cleavage and polyadenylation
specificity factor 73 (CPSF73), the enzyme responsible for cleavage and termination of
messenger RNA (mRNA) genes. We showed that Integrator RNA processing activity is
not only required for noncoding genes but also for protein coding genes facilitating
transcriptional elongation. In this proposal, Aim 1; Will detail the mechanism of the
Integrator regulation of 3’-end processing and termination of protein coding genes. In
Aim 2; We will explore the role of the Integrator complex in regulation of inflammatory
gene expression program following our discovery of cooperative association of Integrator
with RELA, a component of canonical NFkB complex. These findings expand the role for
Integrator in stress signaling and immune system. Finally, in Aim 3; We will elucidate the
function of a new trimeric complex composed of INTS11-INTS9 and BRAT1 protein, a
gene mutated in human developmental syndromes causing rigidity and multifocal
seizure syndrome in neonates and neurodevelopmental disorders.

## Key facts

- **NIH application ID:** 10683065
- **Project number:** 5R01GM078455-11
- **Recipient organization:** UNIVERSITY OF MIAMI SCHOOL OF MEDICINE
- **Principal Investigator:** RAMIN SHIEKHATTAR
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2023
- **Award amount:** $447,858
- **Award type:** 5
- **Project period:** 2010-08-01 → 2026-05-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10683065

## Citation

> US National Institutes of Health, RePORTER application 10683065, Elucidation of Integrator's Function (5R01GM078455-11). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/10683065. Licensed CC0.

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