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The RNA-binding protein Snd1/Tudor-SN regulates hypoxia-responsive gene expression.

Juha Saarikettu1, Saara Lehmusvaara2, Marko Pesu2,3

  • 1Institute of Biotechnology, HiLIFE Helsinki Institute of Life Sciences University of Helsinki Helsinki Finland.

FASEB Bioadvances
|May 8, 2023
PubMed
Summary

The study reveals that the Snd1 protein regulates gene expression and plays a role in the body's adaptation to low oxygen conditions (hypoxia). Snd1 negatively controls hypoxia-induced microRNAs and transcription.

Keywords:
BioIDGene expressionHypoxiaKnockoutSnd1Stress‐reponse

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Area of Science:

  • Molecular Biology
  • Gene Regulation
  • Cellular Stress Response

Background:

  • Snd1 is an evolutionarily conserved RNA-binding protein involved in gene expression regulation.
  • Its precise function in mammalian physiology, particularly under stress, requires further elucidation.

Purpose of the Study:

  • To investigate the physiological consequences of Snd1 gene deletion in mice.
  • To understand Snd1's role in cellular responses, specifically adaptation to hypoxia.
  • To identify proteins interacting with Snd1.

Main Methods:

  • Generation and analysis of Snd1 knockout mice.
  • Transcriptomic analysis (mRNA and microRNA) in spleen and liver.
  • BioID proximity ligation assay in HEK-293T cells.

Main Results:

  • Snd1 knockout mice exhibited reduced fertility, body size, and myeloid cell counts.
  • Gene expression changes in knockout livers mirrored hypoxia adaptation profiles.
  • Upregulation of hypoxia-induced microRNAs (miR-96, -182) was observed in knockout livers.
  • SND1 interactors identified via BioID were predominantly RNA-binding proteins.

Conclusions:

  • Snd1 is not essential for mRNA transcription under normal conditions but is crucial for hypoxia adaptation.
  • Snd1 negatively regulates hypoxia-responsive microRNAs and transcription, acting as a stress response regulator.