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Alexandra Khitun1, Travis J Ness1, Sarah A Slavoff2

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Small open reading frames (smORFs) encode functional polypeptides and regulate gene expression. Recent research reveals that smORF-encoded polypeptides (SEPs) play roles in cellular stress responses across species.

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Area of Science:

  • Genomics
  • Molecular Biology
  • Cellular Biology

Background:

  • Small open reading frames (smORFs) were historically overlooked in genome annotation.
  • Advances in genomics and proteomics have identified thousands of translated smORFs.
  • smORFs can encode functional polypeptides or act as translational regulators.

Purpose of the Study:

  • To review the evidence for smORF-encoded polypeptides (SEPs) in stress responses.
  • To explore the role of upstream ORFs (uORFs) in regulating stress-responsive translation.
  • To highlight a regulated subclass of smORFs and their contribution to cellular homeostasis.

Main Methods:

  • Genomic analysis
  • Ribosome footprinting
  • Proteomic studies
  • Literature review

Main Results:

  • Thousands of translated smORFs have been identified across diverse genomes.
  • Some SEPs are involved in stress responses in both prokaryotes and eukaryotes.
  • Specific uORFs regulate the translation of downstream genes during stress in eukaryotes.

Conclusions:

  • smORFs represent a significant, previously underappreciated, functional component of genomes.
  • SEPs contribute to cellular adaptation and survival under stress conditions.
  • Regulation of translation via smORFs is crucial for maintaining cellular homeostasis.