Viral nucleases reveal an mRNA degradation-transcription feedback loop in mammalian cells
Transcriptomics Dataset
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| Accession | GSE70481 |
| Title | Viral nucleases reveal an mRNA degradation-transcription feedback loop in mammalian cells |
| Description | Gamma-herpesviruses encode a cytoplasmic mRNA-targeting endonuclease, termed SOX, that cleaves the majority of mRNAs within a cell. Cleaved fragments are subsequently degraded by the cellular mRNA degradation machinery. Here, we reveal that mammalian cells respond to this widespread cytoplasmic mRNA decay by altering levels of RNA polymerase II (RNAPII) transcription in the nucleus. Measurements of both RNAPII recruitment to promoters and nascent mRNA synthesis revealed that the majority of affected genes are transcriptionally repressed in SOX-expressing cells. The transcriptional feedback does not occur in response to the initial endonuclease-induced cleavage, but instead to degradation of the cleaved fragments by cellular exonucleases. In particular, Xrn1 catalytic activity is required for transcriptional repression. Notably, viral mRNA transcription escapes decay-induced repression, and this escape requires Xrn1. Collectively, these results indicate that mRNA decay rates impact transcription in mammalian cells, and that gamma-herpesviruses have incorporated this feedback mechanism into their own gene expression strategy. |
| Landing Page | https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE70481 |
| Repository | Gene Expression Omnibus |
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