Metabolomics,Unknown,Transcriptomics,Genomics,Proteomics

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A potential role for snoRNA in PKR activation during metabolic stress

ABSTRACT: PKR (Protein Kinase RNA-activated) is activated by metabolic stress, such as that associated with obesity, and this activation depends on its RNA-binding domain. Here we investigated whether endogenous RNA triggers PKR activation in response to lipid exposure. Our results indicate that snoRNAs (small nucleolar RNAs) associate with PKR during metabolic stress. Our high-throughput sequence shows that snoRNAs are enriched in PKR_WT samples after palmitic acid treatment compared to mock-treated samples. MEF cells reconstituted with wild type PKR (PKR_WT) or PKR with a mutation in each dsRBM (PKR_RM) were mock- or palmitate-treated. RNAs associated with PKR were immunoprecipitated. IPed RNAs were extracted, cloned and sequenced. We performed differential expression to obtain RNAs enriched in PKRWT after palmitate treatment. We sequenced three different datasets of samples (A, B and C). Each A and B dataset contains three biological replicates. Dataset C contains a single sample.

ORGANISM(S): Mus musculus

SUBMITTER: Osama Youssef 

PROVIDER: E-GEOD-66540 | biostudies-arrayexpress |

REPOSITORIES: biostudies-arrayexpress

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Potential role for snoRNAs in PKR activation during metabolic stress.

Youssef Osama A OA   Safran Sarah A SA   Nakamura Takahisa T   Nix David A DA   Hotamisligil Gökhan S GS   Bass Brenda L BL  

Proceedings of the National Academy of Sciences of the United States of America 20150406 16

Protein kinase RNA-activated (PKR) has long been known to be activated by viral double-stranded RNA (dsRNA) as part of the mammalian immune response. However, in mice PKR is also activated by metabolic stress in the absence of viral infection, and this requires a functional kinase domain, as well as a functional dsRNA-binding domain. The endogenous cellular RNA that potentially leads to PKR activation during metabolic stress is unknown. We investigated this question using mouse embryonic fibrobl  ...[more]

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