# Translational Regulation of Embryonic Stem Cell Self-Renewal by Pumlio Proteins

> **NIH NIH R01** · YALE UNIVERSITY · 2020 · $368,500

## Abstract

Project Summary
Stem cells are defined by their unique ability to self-renew meanwhile producing numerous
differentiated cells. How the self-renewal of stem cells is regulated is a central question in stem
cell biology. In recent years, exciting progress has been made in understanding niche signaling
and epigenetic/transcriptional regulation of stem cell self-renewal. However, much less is known
about translational regulation of this process. Among a small number of studies on translational
regulation, most of them are focused on the miRNA-mediated mechanism, which fine-tunes the
temporal- and tissue-specificity of gene expression. Little, if any, is known about whether any
translational regulator serves as a key regulator of the stem cell fate in mammalian systems.
Recent work from my lab indicates that we have discovered two key translational regulators in
mice, called Pumilio (Pum) 1 and Pum 2, that are essential in defining the stem cell fate. Both
Pum1 and Pum2 are expressed in mouse embryonic stem cells (mESCs) and early embryos,
targeting 1,947 and 437 mRNAs in mESCs, respectively. Pum1-Pum2 double mutants are
developmentally delayed at the morula stage and lethal by e8.5; and Pum1-Pum2 double
mutant ESCs fail to self-renew. These exciting findings led us to hypothesize that Pum proteins
are key regulators of ESC self-renewal and thus early embryogenesis. To systematically test
this hypothesis and to explore the role of translational regulation in mammalian stem cells, I
propose to investigate the functions of Pum-mediated translational regulation in mESCs via the
following aims: (1) determine the auto- and inter-regulatory effect of Pum1 and Pum2 in ESCs to
reveal a novel circuitry of gene regulation composed of auto- and inter-regulatory negative
feedback loops and how this circuitry regulates ESC pluripotency, self-renewal, and
differentiation; (2) use combined genomic and proteomic approaches to determine how Pum1
and Pum2 regulate their many target mRNAs in ESCs and how some of the target mRNAs
contribute to ESC pluripotency, self-renewal, and differentiation; (3) determine how Pum1 and
Pum2 interact with other proteins to achieve their regulation of target mRNAs in ESCs. The
proposed study, if achieved, should significantly advance our knowledge on the gene regulation
of stem cell self-renewal. Moreover, it should reveal novel regulatory paradigms and
mechanisms of post-transcriptional regulation as mediated by Pum proteins that are unique to
mammalian systems.

## Key facts

- **NIH application ID:** 9841419
- **Project number:** 5R01GM121386-04
- **Recipient organization:** YALE UNIVERSITY
- **Principal Investigator:** HONGYING QI
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $368,500
- **Award type:** 5
- **Project period:** 2017-01-01 → 2021-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9841419

## Citation

> US National Institutes of Health, RePORTER application 9841419, Translational Regulation of Embryonic Stem Cell Self-Renewal by Pumlio Proteins (5R01GM121386-04). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/9841419. Licensed CC0.

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