# RNA metabolism mediated by the Integrator complex

> **NIH NIH R35** · UNIVERSITY OF FLORIDA · 2020 · $375,314

## Abstract

PROJECT SUMMARY
Project title: RNA metabolism mediated by the Integrator complex
Precise recognition of RNAs by RNA-binding proteins and RNA-specific enzymes is critical for gene expression
and cell growth. In recent years, the Integrator protein complex has emerged as an essential component in
RNA metabolism. Disrupted RNA regulation caused by a malfunctioned Integrator has been implicated in
multiple malignancies, including developmental failure (malformations of cortical development),
neurodegenerative disease (Cornelia de Lange syndrome) and cancer (lung and prostate carcinomas). Yet,
knowledge about the underlying pathological mechanisms is lacking. This is largely due to a limited
understanding of the interplay between Integrator and its RNA substrates.
 We and others found that Integrator is an RNA-specific enzyme that processes several species of
regulatory non-coding RNA (ncRNA). Furthermore, Integrator regulates the generation of mRNAs that are
rapidly activated in response to growth factor stimulation. How Integrator recognizes RNAs through one or
more of its 14 protein subunits is unclear. In the next five years, by developing new biochemical
techniques, we will purify from human cells the key Integrator protein subunits that mediate RNA
recognition and binding. Subsequently, we will use these RNA-recognition subunits to identify the
RNAs that directly bind to, and are processed by, the Integrator complex.
 Our recent data suggest that one of the potential RNAs processed by Integrator are a specific set of
microRNAs, small ncRNA molecules that control the function of other genes and hence are important for
controlling human developmental and disease processes. microRNAs that are processed by Integrator are
special in that they are produced in cells where most of the conventionally-generated microRNAs are not
present. Several of these microRNAs function to suppress the growth of tumors. We will investigate how
these microRNAs are uniquely generated and how they regulate the expression of other genes.
 There is relatively little known about the function of Integrator, how it controls RNA metabolism and how
these RNAs operate within cells. Therefore, our research fills a major gap in knowledge. Our efforts in the next
five years will not only uncover a new class of RNA-binding proteins as important gene regulators, but will also
provide the basis for developing therapeutics to combat diseases that are caused by Integrator deficiency and
dysregulated microRNAs. Techniques and experience acquired in this project will prepare our group for future
research in exploring molecular machineries that generate and regulate RNAs essential for gene expression.

## Key facts

- **NIH application ID:** 9980701
- **Project number:** 5R35GM128753-03
- **Recipient organization:** UNIVERSITY OF FLORIDA
- **Principal Investigator:** MINGYI XIE
- **Activity code:** R35 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $375,314
- **Award type:** 5
- **Project period:** 2018-08-13 → 2023-07-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9980701

## Citation

> US National Institutes of Health, RePORTER application 9980701, RNA metabolism mediated by the Integrator complex (5R35GM128753-03). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/9980701. Licensed CC0.

---

*[NIH grants dataset](/datasets/nih-grants) · CC0 1.0*