# Studies of translational regulatory networks in macrophage-mediated inflammatory responses

> **NIH NIH R21** · MAYO CLINIC ROCHESTER · 2020 · $193,567

## Abstract

PROJECT SUMMARY
 The production of proteins is precisely regulated in innate immune responses, such as the inflammatory
response, to control infection and limit the detrimental effects of inflammation. Malfunction of this regulation
can result in many diseases, such as autoimmune disorders (e.g. rheumatoid arthritis) and inflammatory
diseases (e.g. Crohn's diseases and the inflammatory bowel disease). There are several ways to control how
many proteins a cell produces. For example, cells might regulate how many messenger RNA molecules (also
called mRNAs for short) are produced from a gene, or control how many proteins are translated from those
mRNA molecules. Previous studies of how inflammatory responses are regulated have largely focused on how
mRNA production is controlled. Much less is known about the role that regulating mRNA translation has on the
inflammatory response. Recently, we uncovered widespread regulations of protein synthesis during the
macrophage-mediated inflammatory response by parallel RNA and ribosome profiling on LPS-activated bone
marrow derived macrophages. Specifically, we identified hundreds of differentially translated mRNAs, including
those encoding key inflammatory cytokines, such as TNF, and their 3' untranslated regions have significantly
enriched binding motifs of several RNA-binding proteins. In this study, we will mechanistically dissect the
mRNA translational regulatory networks mediated by one such RNA-binding protein, Cpeb4, which is
associated with human inflammatory bowel disease. Our goals are: a) identify and characterize Cpeb4's target
mRNAs in the activated macrophages; b) determine how Cpeb4 regulates mRNA translation in the
macrophages at molecular level. The results from this study will not only reveal novel mRNA translational
regulatory networks in the macrophage mediated inflammatory response, but also provide molecular
mechanistic insights into how Cpeb4 is involved in the pathogenesis of the inflammatory bowel diseases.

## Key facts

- **NIH application ID:** 9955204
- **Project number:** 5R21AI146431-02
- **Recipient organization:** MAYO CLINIC ROCHESTER
- **Principal Investigator:** Wenqian Hu
- **Activity code:** R21 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $193,567
- **Award type:** 5
- **Project period:** 2019-06-14 → 2022-05-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9955204

## Citation

> US National Institutes of Health, RePORTER application 9955204, Studies of translational regulatory networks in macrophage-mediated inflammatory responses (5R21AI146431-02). Retrieved via AI Analytics 2026-05-27 from https://api.ai-analytics.org/grant/nih/9955204. Licensed CC0.

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