# Mechanisms of mRNA-selective control by Bicaudal-C

> **NIH NIH R01** · UNIVERSITY OF WISCONSIN-MADISON · 2024 · $575,095

## Abstract

Abstract: Over the course of an animal’s lifetime, cell-fate decisions are continually being made
that allow for normal development and growth as well as the health of the adult organism. Cell-
fate decisions require precisely controlled temporal and spatial expression of particular proteins.
In early vertebrate development and certain adult cell types, such as those of the nervous system,
this regulated protein expression relies heavily on post-transcriptional mechanisms, particularly
translational control. This proposal focuses on a conserved RNA binding protein named Bicaudal-
C (Bicc1) that functions in translational regulation and is essential for normal vertebrate
development. While it is established that Bicc1 is an RNA binding protein required for the normal
development and health of vertebrates, the cellular and molecular mechanisms by which Bicc1
performs these roles are largely unknown and thus represent a major gap in knowledge. The long-
term research goal is to define the molecular mechanisms by which developmentally important
RNA binding proteins select their target mRNAs and control mRNA expression to effect specific
cell-fate decisions, and to understand how defects in these processes contribute to cell
dysfunction and organismal disease. The central hypothesis is that Bicc1 selects particular target
mRNAs through a complex RNA binding domain with multiple independent RNA binding surfaces
and regulates translation via additional distinct regions yet to be defined. This hypothesis is based
on extensive research from the lab focused on defining how Bicc1 directs the earliest, maternal
stages of vertebrate development in the model organism Xenopus laevis. This work has
established Bicc1 as a paradigm for understanding how RNA binding proteins control mRNA
translation to direct complex cell-fate decisions. Building on extensive conceptual and technical
progress over the past decade, the Specific Aims will address the central hypothesis by: 1.
Defining how Bicc1 selects its target mRNAs; 2. Defining how Bicc1 represses translation; and 3.
Determining the role of Bicc1 RNA binding and translational repression activities in Xenopus cell-
fate specification. The research employs a rigorous and multidisciplinary strategy incorporating
RNA-protein biochemistry, unique translation-reporter assays, genome-enabled approaches,
reverse molecular genetics, and embryology to define the molecular mechanisms by which the
conserved and disease-relevant RNA binding protein Bicc1 directs the earliest cell-fate decisions
essential for vertebrate development.

## Key facts

- **NIH application ID:** 10981851
- **Project number:** 1R01GM152615-01A1
- **Recipient organization:** UNIVERSITY OF WISCONSIN-MADISON
- **Principal Investigator:** Michael D Sheets
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $575,095
- **Award type:** 1
- **Project period:** 2024-08-01 → 2028-04-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10981851

## Citation

> US National Institutes of Health, RePORTER application 10981851, Mechanisms of mRNA-selective control by Bicaudal-C (1R01GM152615-01A1). Retrieved via AI Analytics 2026-05-25 from https://api.ai-analytics.org/grant/nih/10981851. Licensed CC0.

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