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Stem-loop binding protein and metal carcinogenesis.

Beatrix R Bradford1, Chunyuan Jin1

  • 1Department of Environmental Medicine, New York University Grossman School of Medicine, 341 East 25th Street, New York, NY, 10010, USA.

Seminars in Cancer Biology
|August 20, 2021
PubMed
Summary

Stem-loop binding protein (SLBP) depletion causes histone mRNA misprocessing and polyadenylation, contributing to genomic instability and cancer. Heavy metals like arsenic and nickel can induce SLBP loss, suggesting a role in carcinogenesis.

Keywords:
CarcinogenesisHeavy metalHistonePolyadenylationStem-loop binding protein

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Area of Science:

  • Molecular Biology
  • Cancer Research
  • Toxicology

Background:

  • Canonical histone mRNAs are uniquely processed without polyadenylation, involving stem-loop binding protein (SLBP).
  • SLBP regulates histone mRNA metabolism, including nuclear export, degradation, and translation.
  • Loss of SLBP function leads to histone mRNA polyadenylation, aberrant cell cycle progression, and genomic instability.

Purpose of the Study:

  • To review the regulation of SLBP expression and the consequences of its depletion.
  • To explore SLBP's role in cancer-related endpoints.
  • To focus on heavy metal-induced SLBP depletion and its potential as a mechanism for metal-induced carcinogenesis.

Main Methods:

  • Literature review of studies on SLBP regulation, function, and role in cancer.
  • Analysis of research linking heavy metals to SLBP depletion and histone mRNA misprocessing.
  • Synthesis of evidence connecting SLBP dysfunction to carcinogenesis.

Main Results:

  • SLBP depletion results in canonical histone mRNA polyadenylation and altered histone protein levels.
  • Heavy metal carcinogens (arsenic, nickel) can induce SLBP loss.
  • Polyadenylated histone H3 mRNA is associated with abnormal transcription, cell cycle arrest, genomic instability, and cell transformation.

Conclusions:

  • SLBP depletion is a critical factor in histone mRNA misprocessing and subsequent cellular dysfunction.
  • Metal-induced SLBP depletion represents a potential mechanism for heavy metal-induced carcinogenesis.
  • Targeting SLBP dysfunction may offer new avenues for cancer prevention and therapy.