National Institutes of Health/National Institute of General Medical Sciences (NIH/NIGMS)
R01GM121706
米国
引用
ジャーナル: Science / 年: 2018 タイトル: Dicer uses distinct modules for recognizing dsRNA termini. 著者: Niladri K Sinha / Janet Iwasa / Peter S Shen / Brenda L Bass / 要旨: Invertebrates rely on Dicer to cleave viral double-stranded RNA (dsRNA), and Dicer-2 distinguishes dsRNA substrates by their termini. Blunt termini promote processive cleavage, while 3' overhanging ...Invertebrates rely on Dicer to cleave viral double-stranded RNA (dsRNA), and Dicer-2 distinguishes dsRNA substrates by their termini. Blunt termini promote processive cleavage, while 3' overhanging termini are cleaved distributively. To understand this discrimination, we used cryo-electron microscopy to solve structures of Dicer-2 alone and in complex with blunt dsRNA. Whereas the Platform-PAZ domains have been considered the only Dicer domains that bind dsRNA termini, unexpectedly, we found that the helicase domain is required for binding blunt, but not 3' overhanging, termini. We further showed that blunt dsRNA is locally unwound and threaded through the helicase domain in an adenosine triphosphate-dependent manner. Our studies reveal a previously unrecognized mechanism for optimizing antiviral defense and set the stage for the discovery of helicase-dependent functions in other Dicers.