# Regulation of Tristetraprolin-mediated mRNA decay by signaling pathways in the inflammatory response

> **NIH NIH F31** · UNIVERSITY OF CALIFORNIA, SAN DIEGO · 2020 · $38,395

## Abstract

Project Summary:
The regulation of cytokines is of vital importance for achieving homeostasis following the induction of the innate
immune response; an inability to do so promotes the development of chronic conditions such as auto-immunity
and cancer. Tristetraprolin (TTP) regulates the translation and stability of pro-inflammatory cytokine mRNAs
containing AU-rich elements (AREs) through the recruitment of components involved in translation repression,
deadenylation, decapping, and exonucleolytic degradation. Recently, the C-terminus of TTP has been shown
to be a docking site for the CCR4-NOT deadenylase complex through its association with the scaffold protein
CNOT1. This CNOT1-interacting motif (CIM) of TTP is highly conserved among TTP family members and is a
site of phosphorylation; however, the relevance of this phosphorylation event in TTP regulation is currently
unknown. Deadenylation is often regarded as the rate-limiting step of mRNA decay, suggesting that regulation
of the TTP CIM is a critical checkpoint of the innate immune response. The objective of this research is to i)
understand the effect that cell signaling events, acting on the CIM, have on the inflammatory response, and ii)
investigate the consequence that mutating the CIM will have on target mRNA stability. Furthermore, although it
is generally accepted that the removal of the poly(A) tail is sufficient to promote further mRNA decay,
preliminary work suggest that despite little degradation of a reporter transcript, the TTP CIM is capable of
activating deadenylation. It is possible that for TTP-mediated mRNA degradation to occur, deadenylation must
be coupled with other decay-promoting events. Therefore, an additional goal of this project is to uncover TTP-
domains that, when coupled with the CIM, promote the decay of target transcripts. In order to address these
questions, a combination of molecular biology, human-based cell culture, mass-spectrometry, and next-
generation sequencing techniques will be performed. The work proposed here offers insight into both the
regulation of the inflammatory response in addition to offering insight into the mechanisms involving mRNA
decay.

## Key facts

- **NIH application ID:** 9851282
- **Project number:** 5F31GM128320-02
- **Recipient organization:** UNIVERSITY OF CALIFORNIA, SAN DIEGO
- **Principal Investigator:** Alberto Carreno
- **Activity code:** F31 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $38,395
- **Award type:** 5
- **Project period:** 2019-01-01 → 2021-12-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9851282

## Citation

> US National Institutes of Health, RePORTER application 9851282, Regulation of Tristetraprolin-mediated mRNA decay by signaling pathways in the inflammatory response (5F31GM128320-02). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/9851282. Licensed CC0.

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