Knock-down of heterogeneous nuclear ribonucleoprotein a1 results in neurite damage, altered stress granule biology, and cellular toxicity in differentiated neuronal cells

Amber Anees, Hannah E. Salapa, Patricia A. Thibault, Catherine Hutchinson, S. Austin Hammond, Michael C. Levin

Research output: Contribution to journalArticlepeer-review

3 Scopus citations

Abstract

Heterogeneous nuclear ribonucleoprotein A1 (hnRNP A1) is an RNA binding protein (RBP) that is localized within neurons and plays crucial roles in RNA metabolism. Its importance in neuronal functioning is underscored from the study of its pathogenic features in many neurodegenerative diseases where neuronal hnRNP A1 is mislocalized from the nucleus to the cytoplasm resulting in loss of hnRNP A1 function. Here, we model hnRNP A1 loss-of-function by siRNA-mediated knock-down in differentiated Neuro-2a cells. Through RNA sequencing (RNA-seq) followed by gene ontology (GO) analyses, we show that hnRNP A1 is involved in important biological processes, including RNA metab-olism, neuronal function, neuronal morphology, neuronal viability, and stress granule (SG) formation. We further con-firmed several of these roles by showing that hnRNP A1 knock-down results in a reduction of neurite outgrowth, increase in cell cytotoxicity and changes in SG formation. In summary, these findings indicate that hnRNP A1 loss-of-function contributes to neuronal dysfunction and cell death and implicates hnRNP A1 dysfunction in the pathoge-nesis of neurodegenerative diseases.

Original languageEnglish
Article numberENEURO.0350-21.2021
JournaleNeuro
Volume8
Issue number6
DOIs
StatePublished - 1 Nov 2021
Externally publishedYes

Keywords

  • Heterogeneous nuclear ribonucleoprotein A1
  • Neuro-2a cell line
  • Neurodegenerative disease
  • Neuronal cell damage
  • RNA binding protein
  • Small interfering RNA

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