# Diverse and dynamically regulated mRNP composition regulating translation

> **NIH NIH R01** · UNIVERSITY OF CALIFORNIA BERKELEY · 2024 · $299,391

## Abstract

ABSTRACT
Cells tightly regulate translation initiation in order to control which proteins they synthesize and
how much of each protein they produce. This regulation of protein synthesis matches translation
levels with the cell's translational capacity and physiological needs. Translation initiation, in
particular, is a key point for both global and transcript-specific regulation. In the canonical
pathway for translation initiation, an mRNA is first activated by the formation of a closed-loop
complex bridging between the 5'-methylguanosine cap and the 3'-polyadenylate tail. A small
ribosomal subunit, accompanied by a variety of other initiation factors, is recruited to the mRNA
and scans in order to begin translation at the first AUG.
Recent evidence suggests that translation initiation does not proceed down such a uniform
pathway. Individual translation factors are subject to regulation downstream of major signaling
pathways, including MAP kinase cascades, mTOR kinase signaling, and the integrated stress
response. Activation or inhibition of core translation initiation factors can produce transcript-
specific changes in translation, leading to broad translational reprogramming. Translation of
developmentally regulated genes also depends on cryptic initiation factors such as eIF2A,
eIF2D, and DENR/MCTS-1.
Our motivating hypothesis is that this heterogeneous landscape of translation initiation
complexes underlies dynamic, mRNA-specific control of protein synthesis. Here, we propose to
use proximity labeling of protein and RNA in order to survey the composition of translation
initiation complexes that assemble in vivo and understanding how this changes in response to
physiological and environmental signals. We will couple this with an analysis of translational
across the transcriptome. Together, these results will reveal the full diversity of pathways for
translation initiation in vivo and show how these different pathways mediate translational
expression programs.

## Key facts

- **NIH application ID:** 10813177
- **Project number:** 5R01GM139008-02
- **Recipient organization:** UNIVERSITY OF CALIFORNIA BERKELEY
- **Principal Investigator:** NICHOLAS T INGOLIA
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $299,391
- **Award type:** 5
- **Project period:** 2023-04-01 → 2027-01-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10813177

## Citation

> US National Institutes of Health, RePORTER application 10813177, Diverse and dynamically regulated mRNP composition regulating translation (5R01GM139008-02). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10813177. Licensed CC0.

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