RNA解旋酶A
干扰素
DNA
重组DNA
生物
野生型
解旋酶
突变体
Ⅰ型干扰素
分子生物学
细胞生物学
化学
基因
病毒学
核糖核酸
生物化学
作者
Ravi Shankar Singh,Venkatasubramanian Vidhyasagar,Shizhuo Yang,Ananna Bhadra Arna,Manisha Yadav,Aanchal Aggarwal,Alexya N. Aguilera,Satoru Shinriki,Kalpana K. Bhanumathy,Kannupriya Pandey,Aizhang Xu,Noreen Rapin,Mark Bosch,John F. DeCoteau,Jim Xiang,Franco J. Vizeacoumar,Yan Zhou,Vikram Misra,Hirotaka Matsui,Susan R. Ross,Yuliang Wu
出处
期刊:Cell Reports
[Elsevier]
日期:2022-05-01
卷期号:39 (8): 110856-110856
被引量:37
标识
DOI:10.1016/j.celrep.2022.110856
摘要
Upon binding double-stranded DNA (dsDNA), cyclic GMP-AMP synthase (cGAS) is activated and initiates the cGAS-stimulator of IFN genes (STING)-type I interferon pathway. DEAD-box helicase 41 (DDX41) is a DEAD-box helicase, and mutations in DDX41 cause myelodysplastic syndromes (MDSs) and acute myeloid leukemia (AML). Here, we show that DDX41-knockout (KO) cells have reduced type I interferon production after DNA virus infection. Unexpectedly, activations of cGAS and STING are affected in DDX41 KO cells, suggesting that DDX41 functions upstream of cGAS. The recombinant DDX41 protein exhibits ATP-dependent DNA-unwinding activity and ATP-independent strand-annealing activity. The MDS/AML-derived mutant R525H has reduced unwinding activity but retains normal strand-annealing activity and stimulates greater cGAS dinucleotide-synthesis activity than wild-type DDX41. Overexpression of R525H in either DDX41-deficient or -proficient cells results in higher type I interferon production. Our results have led to the hypothesis that DDX41 utilizes its unwinding and annealing activities to regulate the homeostasis of dsDNA and single-stranded DNA (ssDNA), which, in turn, regulates cGAS-STING activation.
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