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Loss of the histone pre-mRNA processing factor stem-loop binding protein in Drosophila causes genomic instability and

Harmony R Salzler1, Jean M Davidson, Nathan D Montgomery

  • 1Curriculum in Genetics and Molecular Biology, University of North Carolina, Chapel Hill, North Carolina, United States of America.

Plos One
|December 10, 2009
PubMed
Abstract

Insights

Stem-loop Binding Protein (SLBP) is crucial for histone mRNA processing. Its absence in Drosophila causes genomic instability and developmental defects, highlighting its role in organism fitness.

Area of Science:

  • Molecular Biology
  • Genetics
  • Developmental Biology

Background:

  • Replication-dependent histone mRNAs have a unique stem-loop 3' end structure, unlike typical polyadenylated mRNAs.
  • Stem-loop Binding Protein (SLBP) is essential for processing this structure and regulating histone mRNA metabolism.
  • The in vivo significance of the histone mRNA 3' end stem-loop for organism fitness and genome maintenance was previously uncharacterized.

Purpose of the Study:

  • To investigate the in vivo role of SLBP in Drosophila melanogaster.
  • To determine the consequences of disrupted histone mRNA 3' end processing on genome maintenance and organism fitness.

Main Methods:

  • Analysis of Slbp gene disruption in Drosophila.
  • Assessment of histone pre-mRNA processing and polyadenylation.
  • Evaluation of genomic instability markers (LOH, chromosome breaks, tetraploidy, PEV).
  • Examination of cell proliferation and S phase progression in Slbp mutant cells.

Main Results:

  • Slbp disruption led to aberrant histone pre-mRNA processing, producing polyadenylated histone mRNAs.
  • Slbp mutants exhibited significant genomic instability, including loss of heterozygosity and chromosome breaks.
  • Mutant cells displayed tetraploidy, altered position effect variegation, S phase defects, and slower proliferation.
  • Developmental defects were observed in Slbp mutant imaginal discs.

Conclusions:

  • The histone mRNA 3' end stem-loop, mediated by SLBP, is critical for proper replication-coupled histone mRNA biosynthesis.
  • Disruption of this process leads to altered chromatin assembly and subsequent genomic instability.
  • Impaired histone mRNA metabolism impacts cell proliferation, development, and overall organism fitness.

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