# Histone mRNA Regulation in Development

> **NIH NIH R01** · UNIV OF NORTH CAROLINA CHAPEL HILL · 2020 · $610,981

## Abstract

ABSTRACT
Proper regulation of histone biosynthesis during the cell cycle is critical for the
appropriate coordination of chromatin assembly and DNA replication. Overproduction or
underproduction of histone protein results in replication stress and genome instability
that contributes to the development of cancer. In this proposal we undertake a
comprehensive analysis of replication-dependent (RD) histone mRNA biosynthesis and
how this process is coordinated with the cell cycle. Animal RD-histone mRNAs are the
only eukaryotic mRNAs that lack a polyA tail, ending instead in a conserved stem loop
structure. In contrast, mRNAs for histone variants such as H3.3 and H2A.Z are encoded
by polyadenylated mRNAs. Generation of the unique RD-histone mRNA 3' end results
from the activity of an evolutionary conserved set of pre-RNA processing factors. The
genes encoding all five RD-histone proteins are clustered in metazoan genomes, and
transcription and pre-mRNA processing factors required for histone mRNA biosynthesis
are organized into a nuclear body (the histone locus body or HLB) that assembles at
these gene clusters. We will determine the requirements for the coordinate synthesis of
the RD-histone mRNAs using both biochemical and genetic approaches in Drosophila,
with a particular focus on the role that the HLB plays in histone transcription and pre-
mRNA processing. Histone gene clusters provide a system in which one can readily
study the expression of a tightly regulated set of genes at all levels of mRNA
biosynthesis, from the organization of genes within the nucleus through activation of
transcription, pre-mRNA processing and transcription termination. Our Drosophila
experimental paradigm permits the in vivo interrogation of these fundamental processes
in gene expression in ways that are unavailable to other systems.

## Key facts

- **NIH application ID:** 9829109
- **Project number:** 5R01GM058921-20
- **Recipient organization:** UNIV OF NORTH CAROLINA CHAPEL HILL
- **Principal Investigator:** Robert J Duronio
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $610,981
- **Award type:** 5
- **Project period:** 1999-05-01 → 2020-11-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9829109

## Citation

> US National Institutes of Health, RePORTER application 9829109, Histone mRNA Regulation in Development (5R01GM058921-20). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/9829109. Licensed CC0.

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