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Details on Person HHV8 ORF57 directly binds the cellular export adaptor ALYREF...

Class:IdSummation:9991376
_displayNameHHV8 ORF57 directly binds the cellular export adaptor ALYREF...
_timestamp2026-06-04 17:29:36
created[InstanceEdit:9991336] Stephan, Ralf, 2026-06-04
textHHV8 ORF57 directly binds the cellular export adaptor ALYREF and tethers it to viral intronless transcripts already associated with the cap-binding complex (CBC), generating an ORF57:ALYREF:CBC:viral mRNA ribonucleoprotein. A direct, RNase-resistant ORF57-ALYREF interaction was demonstrated by GST pull-down with recombinant proteins and co-immunoprecipitation from TPA-induced BCBL-1 cells, with the N-terminal region of ORF57 contacting the N- and C-terminal conserved domains of ALYREF (Malik et al. 2004). RNA immunoprecipitation from cells co-expressing ORF57 with intronless HHV8 ORF47 or gB transcripts showed that ALYREF associates with these viral mRNAs only when ORF57 is present, and a PxxP motif mutation (P208A/P211A) that abolishes ORF57-ALYREF binding also abolishes ALYREF recruitment to the viral RNA without affecting ORF57's own RNA binding (Boyne et al. 2008); the same ALYREF-binding-defective mutant fails to co-precipitate ALYREF (Li et al. 2012). UV cross-linking further established that ALYREF contacts viral RNA directly and preferentially near the 5′ end in an ORF57- and ORE-dependent manner (Stubbs et al. 2012), and the ORF57-ALYREF interaction is preserved across independent studies even where downstream export function is disputed (Pilkington et al. 2012).

Alternatively, ORF57 can also bind to the export adaptor FYTTD1. ALYREF acts as a negative regulator of this binding event, since competitive GST pull-downs and dose-dependent co-immunoprecipitations showed that increasing ALYREF displaces FYTTD1 from ORF57, whereas FYTTD1 only weakly displaces ALYREF, indicating that ORF57 preferentially engages ALYREF and binds FYTTD1 when ALYREF is depleted (Jackson et al. 2011).
(summation)[Reaction:9991406] ORF57 recruits ALYREF to mRNA [Homo sapiens]
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