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TitleDicer uses distinct modules for recognizing dsRNA termini.
Journal, issue, pagesScience, Vol. 359, Issue 6373, Page 329-334, Year 2018
Publish dateJan 19, 2018
AuthorsNiladri K Sinha / Janet Iwasa / Peter S Shen / Brenda L Bass /
PubMed AbstractInvertebrates 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.
External linksScience / PubMed:29269422 / PubMed Central
MethodsEM (single particle)
Resolution6.8 - 8.7 Å
Structure data

7290

6bu9

EMDB-7290, PDB-6bu9:
Drosophila Dicer-2 bound to blunt dsRNA
Method: EM (single particle) / Resolution: 6.8 Å

7291

6bua

EMDB-7291, PDB-6bua:
Drosophila Dicer-2 apo homology model (helicase, Platform-PAZ, RNaseIII domains)
Method: EM (single particle) / Resolution: 7.1 Å

EMDB-7292:
Drosophila Dicer-2 (apo, intact helicase density)
Method: EM (single particle) / Resolution: 8.7 Å

Source
  • drosophila melanogaster (fruit fly)
  • unidentified (others)
Keywordsrna binding protein/rna / Dicer / Dcr2 / Dcr-2 / dmDcr-2 / Dicer-2 / helicase / dsRNA / RNA / RNA BINDING PROTEIN / rna binding protein-rna complex / dmDcr2 / platform / PAZ / RNAseIII

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