Suppression of methylation-mediated transcriptional gene silencing by βC1-SAHH protein interaction during geminivirus-betasatellite infection.
DNA methylation is a fundamental epigenetic modification that regulates gene expression and represses endogenous transposons and invading DNA viruses. As a counter-defense, the geminiviruses encode proteins that inhibit methylation and transcriptional gene silencing (TGS). Some geminiviruses have acquired a betasatellite called DNA β. This study presents evidence that suppression of methylation-mediated TGS by the sole betasatellite-encoded protein, βC1, is crucial to the association of Tomato yellow leaf curl China virus (TYLCCNV) with its betasatellite (TYLCCNB). We show that TYLCCNB complements Beet curly top virus (BCTV) L2⁻ mutants deficient for methylation inhibition and TGS suppression, and that cytosine methylation levels in BCTV and TYLCCNV genomes, as well as the host genome, are substantially reduced by TYLCCNB or βC1 expression. We also demonstrate that while TYLCCNB or βC1 expression can reverse TGS, TYLCCNV by itself is ineffective. Thus its AC2/AL2 protein, known to have suppression activity in other geminiviruses, is likely a natural mutant in this respect. A yeast two-hybrid screen of candidate proteins, followed by bimolecular fluorescence complementation analysis, revealed that βC1 interacts with S-adenosyl homocysteine hydrolase (SAHH), a methyl cycle enzyme required for TGS. We further demonstrate that βC1 protein inhibits SAHH activity in vitro. That βC1 and other geminivirus proteins target the methyl cycle suggests that limiting its product, S-adenosyl methionine, may be a common viral strategy for methylation interference. We propose that inhibition of methylation and TGS by βC1 stabilizes geminivirus/betasatellite complexes.
State Key Laboratory of Rice Biology, Institute of Biotechnology, Zhejiang University, Hangzhou, People's Republic of China.
Xiuling
X
Yang
Yan
Y
Xie
Priya
P
Raja
Sizhun
S
Li
Jamie N
JN
Wolf
Qingtang
Q
Shen
David M
DM
Bisaro
Xueping
X
Zhou
D043383:Adenosylhomocysteinase / Q000235:genetics* / Q000378:metabolism; D053839:Begomovirus / Q000235:genetics* / Q000378:metabolism / Q000472:pathogenicity; D019175:DNA Methylation; D015971:Gene Expression Regulation, Enzymologic; D015967:Gene Expression Regulation, Viral; D020868:Gene Silencing; D054884:Host-Pathogen Interactions; D010935:Plant Diseases / Q000235:genetics / Q000821:virology; D012526:Satellite Viruses / Q000235:genetics* / Q000378:metabolism / Q000472:pathogenicity; D014158:Transcription, Genetic; D020798:Two-Hybrid System Techniques; D014764:Viral Proteins / Q000378:metabolism
D014764:Viral Proteins; D043383:Adenosylhomocysteinase