NAT10-dependent N⁴-acetylcytidine modification mediates PAN RNA stability, KSHV reactivation, and IFI16-related inflammasome activation.

ABSTRACT: N-acetyltransferase 10 (NAT10) is an N⁴-acetylcytidine (ac⁴C) writer that catalyzes RNA acetylation at cytidine N⁴ position on tRNAs, rRNAs and mRNAs. Recently, NAT10 and the associated ac⁴C have been reported to increase the stability of HIV-1 transcripts. Here, we show that NAT10 catalyzes ac⁴C addition to the polyadenylated nuclear RNA (PAN), a long non-coding RNA encoded by the oncogenic DNA virus Kaposi's sarcoma-associated herpesvirus (KSHV), triggering viral lytic reactivation from latency. Mutagenesis of ac⁴C sites in PAN RNA in the context of KSHV infection abolishes PAN ac⁴C modifications, downregulates the expression of viral lytic genes and reduces virion production. NAT10 knockdown or mutagenesis eras

SUBMITTER: Yan Q 

PROVIDER: S-EPMC10564894 | biostudies-literature | 2023 Oct

REPOSITORIES: biostudies-literature