STAU1 selectively regulates the expression of inflammatory and immune response genes and alternative splicing of the nerve growth factor receptor signaling pathway

Oncol Rep. 2020 Nov;44(5):1863-1874. doi: 10.3892/or.2020.7769. Epub 2020 Sep 16.

Abstract

Double‑stranded RNA‑binding protein Staufen homolog 1 (STAU1) is a highly conserved multifunctional double‑stranded RNA‑binding protein, and is a key factor in neuronal differentiation. RNA sequencing was used to analyze the overall transcriptional levels of the upregulated cells by STAU1 and control cells, and select alternative splicing (AS). It was determined that the high expression of STAU1 led to changes in the expression levels of a variety of inflammatory and immune response genes, including IFIT2, IFIT3, OASL, and CCL2. Furthermore, STAU1 was revealed to exert a significant regulatory effect on the AS of genes related to the 'nerve growth factor receptor signaling pathway'. This is of significant importance for neuronal survival, differentiation, growth, post‑damage repair, and regeneration. In conclusion, overexpression of STAU1 was associated with immune response and regulated AS of pathways related to neuronal growth and repair. In the present study, the whole transcriptome of STAU1 expression was first analyzed, which laid a foundation for further understanding the key functions of STAU1.

Keywords: double-stranded RNA-binding protein Staufen homolog 1; RNA-sequencing; alternative splicing; nerve growth factor receptor signaling pathway.

MeSH terms

  • 2',5'-Oligoadenylate Synthetase / genetics
  • 3' Untranslated Regions
  • Alternative Splicing*
  • Apoptosis Regulatory Proteins / genetics
  • Cell Differentiation / genetics
  • Chemokine CCL2 / genetics
  • Cytoskeletal Proteins / metabolism*
  • HeLa Cells
  • Humans
  • Intracellular Signaling Peptides and Proteins / genetics
  • Neurons / physiology
  • RNA, Double-Stranded / metabolism*
  • RNA-Binding Proteins / genetics
  • RNA-Binding Proteins / metabolism*
  • RNA-Seq
  • Receptors, Nerve Growth Factor / metabolism*
  • Signal Transduction / genetics
  • Signal Transduction / immunology
  • Up-Regulation / immunology

Substances

  • 3' Untranslated Regions
  • Apoptosis Regulatory Proteins
  • CCL2 protein, human
  • Chemokine CCL2
  • Cytoskeletal Proteins
  • IFIT2 protein, human
  • IFIT3 protein, human
  • Intracellular Signaling Peptides and Proteins
  • RNA, Double-Stranded
  • RNA-Binding Proteins
  • Receptors, Nerve Growth Factor
  • STAU1 protein, human
  • OASL protein, human
  • 2',5'-Oligoadenylate Synthetase