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September 9, 2014BMC Cell BiologyOpen Access

Mitochondrial localization of the OAS1 p46 isoform associated with a common single nucleotide polymorphism

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Key result

The OAS1 SNP rs10774671 determines differential expression of OAS1 isoforms, with the p46 isoform localizing to the mitochondria and the p42 isoform localizing primarily to cytoplasmic vacuoles.

Population

Three human cell lines (HeLa, HT1080, Daudi) with different genotypes in the OAS1 SNP rs10774671

Design

Preclinical

Authors

KKKarina Hansen KjærIan's Friends FoundationJPJytte PahusVIA University CollegeMHMariann Fagernæs HansenAarhus University

Discussion

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Implication

Mitochondrial OAS1 p46 localization suggests organelle-specific innate immunity; leaves open human validation and disease relevance.

Structured PICO

P
Population
Three human cell lines (HeLa, HT1080, Daudi) with different genotypes in the OAS1 SNP rs10774671
E
Exposure
Type 1 interferon treatment and recombinantly expressed OAS1 mutant proteins
O
Outcome
Expression and localization of OAS1 isoforms, and enzymatic OAS1 activitysurrogate

The OAS1 p46 isoform, associated with the G allele of SNP rs10774671, localizes to the mitochondria, indicating the presence of a full 2-5A system in mitochondria.

Limitations

  • The contribution of OAS2 and OAS3 proteins to total OAS activity in the cell lines is not clear
  • The hypotheses regarding sustained OAS activity and apoptosis due to mitochondrial localization are speculative

Cite This Study

Kjær et al. (2014) studied this question. OAS1 SNPs rs10774671 and rs1131454 was evaluated on OAS1 isoform expression and cellular localization. The OAS1 SNP rs10774671 determines differential expression of OAS1 isoforms, with the p46 isoform localizing to the mitochondria and the p42 isoform localizing primarily to cytoplasmic vacuoles.

synapsesocial.com/papers/6aa2776948edd87d04240991https://doi.org/10.1186/1471-2121-15-33
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