Model of ORF57-mediated protection of KSHV transcripts.

(A) In the absence of ORF57, hMTR4 interacts with ARS2 and recruits the nuclear exosome to viral transcripts to degrade them. (B) When ORF57 is expressed, it directly binds to viral transcripts and recruits the export adaptor ALYREF. The ORF57 recruitment of ALYREF allows it to outcompete hMTR4 for ARS2 binding to protect viral transcripts from exosome-mediated degradation. (C) For ALYREF-independent, ORF57-dependent RNAs (e.g. ORF8 and ORF9), we speculate that ORF57 recruits an unknown cellular factor(s) (black square) which prevents hMTR4 recruitment to viral RNAs. See text for more details. For simplicity, PPD factors were omitted from the diagram.