MicroRNA profiling in HEK293T cells after NDV infection
Ontology highlight
ABSTRACT:
ORGANISM(S): synthetic construct Homo sapiens
PROVIDER: GSE65694 | GEO | 2015/02/07
SECONDARY ACCESSION(S): PRJNA274735
REPOSITORIES: GEO
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Project description:RIG-I like receptors (RLRs) are the major viral RNA sensors essential for the initiation of antiviral immune responses to numerous RNA viruses. RLRs are subjected to stringent transcriptional and posttranslational regulations, of which ubiquitination is one of the most important. However, the role of ubiquitination in RLR transcription is unknown. Here, we generated, screened 375 definite ubiquitin ligase knockout cell lines and identified UBR5 as a positive regulator of RLR transcription. UBR5 deficiency (UBR5-/-) reduced antiviral immune responses to RNA viruses, while increased viral replication in primary cells and mice. Ubr5-/- mice were more susceptible to lethal RNA virus infection than Ubr5+/+ littermates. Mechanistically, UBR5 mediated the Lysine 63-linked ubiquitination of TRIM28, an epigenetic repressor of RLRs. This modification prevented intramolecular SUMOylation of TRIM28, thus disengaged the TRIM28-imposed brake on RLR transcription. In sum, UBR5 enables rapid upregulation of RLR expression to boost antiviral immune responses by ubiquitinating and de-SUMOylating TRIM28.
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Project description:RIG-I like receptors (RLRs) are the major viral RNA sensors essential for the initiation of antiviral immune responses to numerous RNA viruses. RLRs are subjected to stringent transcriptional and posttranslational regulations, of which ubiquitination is one of the most important. However, the role of ubiquitination in RLR transcription is unknown. Here, we generated, screened 375 definite ubiquitin ligase knockout cell lines and identified UBR5 as a positive regulator of RLR transcription. UBR5 deficiency (UBR5-/-) reduced antiviral immune responses to RNA viruses, while increased viral replication in primary cells and mice. Ubr5-/- mice were more susceptible to lethal RNA virus infection than Ubr5+/+ littermates. Mechanistically, UBR5 mediated the Lysine 63-linked ubiquitination of TRIM28, an epigenetic repressor of RLRs. This modification prevented intramolecular SUMOylation of TRIM28, thus disengaged the TRIM28-imposed brake on RLR transcription. In sum, UBR5 enables rapid upregulation of RLR expression to boost antiviral immune responses by ubiquitinating and de-SUMOylating TRIM28.
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