# Histone mRNA Regulation in Development

> **NIH NIH R01** · UNIV OF NORTH CAROLINA CHAPEL HILL · 2021 · $645,564

## Abstract

ABSTRACT
Proper regulation of histone biosynthesis during the cell cycle is critical for coordinating
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
regulated during the cell cycle in the context of animal development. RD-histone mRNAs
are the only eukaryotic mRNAs in animal cells 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 that are not cell cycle regulated.
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 in other experimental systems.

## Key facts

- **NIH application ID:** 10130189
- **Project number:** 2R01GM058921-21
- **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:** 2021
- **Award amount:** $645,564
- **Award type:** 2
- **Project period:** 1999-05-01 → 2024-11-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10130189

## Citation

> US National Institutes of Health, RePORTER application 10130189, Histone mRNA Regulation in Development (2R01GM058921-21). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10130189. Licensed CC0.

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