TY - JOUR
T1 - Dicer functions transcriptionally and posttranscriptionally in a multilayer antiviral defense
AU - Ida Bagus, Andika
AU - Kondo, Hideki
AU - Suzuki, Nobuhiro
N1 - Funding Information:
ACKNOWLEDGMENTS. We thank Drs. Donald L. Nuss and Satoko Kanematsu for the generous gift of the fungal/viral strains, Drs. Shota Nakamura, Daisuke Motooka, and Daisuke Okazaki for fruitful discussion, and the Next-Generation Sequencing core facility of the Genome Information Research Center at the Research Institute for Microbial Diseases of Osaka University for support in RNA sequencing.This study was supported in part by Yomogi, Inc. (N.S.) and Grants-in-Aid for Scientific Research (A) and Innovative Areas from the Japanese Ministry of Education, Culture, Sports, Science, and Technology (KAKENHI 25252011, 17H01463, 16H06436, 16H06429, and 16K21723 to N.S. and H.K.).
Publisher Copyright:
© 2019 National Academy of Sciences. All Rights Reserved.
PY - 2019/2/5
Y1 - 2019/2/5
N2 - In antiviral RNA interference (RNAi), Dicer plays a primary role in processing double-stranded RNA (dsRNA) molecules into small-interfering RNAs (siRNAs) that guide Argonaute effectors to posttranscriptional suppression of target viral genes. Here, we show a distinct role for Dicer in the siRNA-independent transcriptional induction of certain host genes upon viral infection in a filamentous fungus. Previous studies have shown that the two key players, dicer-like 2 (dcl2) and argonaute-like 2 (agl2), of antiviral RNAi in a phytopathogenic ascomycete, Cryphonectria parasitica, are highly transcriptionally induced upon infection with certain RNA mycoviruses, including the positive-stranded RNA hypovirus mutant lacking the RNAi suppressor (Cryphonectria hypovirus 1-Δp69, CHV1-Δp69). This induction is regulated by the Spt-Ada-Gcn5 acetyltransferase (SAGA) complex, a well-known transcriptional coactivator. The present study shows that diverse host genes, in addition to dcl2 and agl2, were up-regulated more than 10-fold by SAGA upon infection with CHV1-Δp69. Interestingly, DCL2, but not AGL2, was essential for SAGA-mediated global gene up-regulation. Moreover, deletion of certain virus-induced genes enhanced a CHV1-Δp69 symptom (growth rate) but not its accumulation. Constitutive, modest levels of dcl2 expression drastically reduced viral siRNA accumulation but were sufficient for full-scale up-regulation of host genes, suggesting that high induction of dcl2 and siRNA production are not essential for the transcriptional up-regulation function of DCL2. These data clearly demonstrate the dual functionality of DCL2: as a dsRNA-specific nuclease in post-transcriptional antiviral RNA silencing and as a key player in SAGAmediated host gene induction, which independently represses viral replication and alleviates virus-induced symptom expression.
AB - In antiviral RNA interference (RNAi), Dicer plays a primary role in processing double-stranded RNA (dsRNA) molecules into small-interfering RNAs (siRNAs) that guide Argonaute effectors to posttranscriptional suppression of target viral genes. Here, we show a distinct role for Dicer in the siRNA-independent transcriptional induction of certain host genes upon viral infection in a filamentous fungus. Previous studies have shown that the two key players, dicer-like 2 (dcl2) and argonaute-like 2 (agl2), of antiviral RNAi in a phytopathogenic ascomycete, Cryphonectria parasitica, are highly transcriptionally induced upon infection with certain RNA mycoviruses, including the positive-stranded RNA hypovirus mutant lacking the RNAi suppressor (Cryphonectria hypovirus 1-Δp69, CHV1-Δp69). This induction is regulated by the Spt-Ada-Gcn5 acetyltransferase (SAGA) complex, a well-known transcriptional coactivator. The present study shows that diverse host genes, in addition to dcl2 and agl2, were up-regulated more than 10-fold by SAGA upon infection with CHV1-Δp69. Interestingly, DCL2, but not AGL2, was essential for SAGA-mediated global gene up-regulation. Moreover, deletion of certain virus-induced genes enhanced a CHV1-Δp69 symptom (growth rate) but not its accumulation. Constitutive, modest levels of dcl2 expression drastically reduced viral siRNA accumulation but were sufficient for full-scale up-regulation of host genes, suggesting that high induction of dcl2 and siRNA production are not essential for the transcriptional up-regulation function of DCL2. These data clearly demonstrate the dual functionality of DCL2: as a dsRNA-specific nuclease in post-transcriptional antiviral RNA silencing and as a key player in SAGAmediated host gene induction, which independently represses viral replication and alleviates virus-induced symptom expression.
KW - Antiviral defense
KW - Cryphonectria parasitica
KW - Fungal virus
KW - RNA silencing
KW - SAGA
UR - http://www.scopus.com/inward/record.url?scp=85061117940&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=85061117940&partnerID=8YFLogxK
U2 - 10.1073/pnas.1812407116
DO - 10.1073/pnas.1812407116
M3 - Article
C2 - 30674672
AN - SCOPUS:85061117940
VL - 116
SP - 2274
EP - 2281
JO - Proceedings of the National Academy of Sciences of the United States of America
JF - Proceedings of the National Academy of Sciences of the United States of America
SN - 0027-8424
IS - 6
ER -