# Polyadenylation and Translational Control

> **NIH NIH R01** · UNIV OF MASSACHUSETTS MED SCH WORCESTER · 2020 · $57,819

## Abstract

7. Project Summary/Abstract
The broad objective of thus proposal is to understand posttranscriptional control of early
animal development. One mechanism that regulates maternal mRNA expression is
cytoplasmic polyadenylation. CPEB, a sequence-specific RNA binding protein, is at the
heart of this process; it nucleates a number of factors on specific mRNAs and controls
translation by modulating poly(A) tail length. Polyadenylation does not happen en
masse, but instead occurs in sequential waves that are most evident during oocyte
maturation in Xenopus. The first wave happens at meiosis I (MI) while the second
occurs at meiosis II (MII). One determinant for first or second wave polyadenylation is
the amount of CPEB in the cell. During the MI to MII transition, some of the CPEB is
destroyed, which is important for second wave polyadenylation. CPEB destruction
requires multiple cdk1 phosphorylations, subsequent ubiquitination, and Pin1
(peptidylprolyl cis/trans isomerase) activity. Pin1 activity increases during meiosis and
binds and controls CPEB destruction. Moreover, Pin1 mediates CPEB destruction in
mammalian cells as well. Pin1 also binds phospho-maskin, the CPEB- and eIF4E-
binding factor that coincides with maskin phosphorylation and dissociation from eIF4E,
allowing initiation complex assembly. The goals of the first specific aim are to determine
how Pin1 mediates CPEB destruction and MI to MII transitioning, and whether it
regulates translation by disrupting the maskin-eIF4E interaction. The second specific
aim intends construct an integrated network map of polyadenylation during maturation.
To do so, CLIP (crosslink IP) will be employed; it will identify not only the mRNAs to
which CPEB binds, but where on the mRNA CPEB binds. This analysis will define, on a
genome wide scale, what constitutes a CPEB binding element (CPE). These
experiments will be complemented by the identification of all the mRNAs that undergo
cytoplasmic polyadenylation, and which of 2 non-canonical poly(A) polymerases are
used. Translational control by CPEB regulates not only early development, but neuronal
synaptic cellular senescence as well. Thus, these experiments have important
implications of human infertility, neurodegeneration, and cancer etiology.

## Key facts

- **NIH application ID:** 10085096
- **Project number:** 3R01GM046779-27S1
- **Recipient organization:** UNIV OF MASSACHUSETTS MED SCH WORCESTER
- **Principal Investigator:** Joel D Richter
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $57,819
- **Award type:** 3
- **Project period:** 1992-02-01 → 2023-01-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10085096

## Citation

> US National Institutes of Health, RePORTER application 10085096, Polyadenylation and Translational Control (3R01GM046779-27S1). Retrieved via AI Analytics 2026-05-26 from https://api.ai-analytics.org/grant/nih/10085096. Licensed CC0.

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