Summary information and primary citation
- PDB-id
-
8yih;
DSSR-derived features in text and
JSON formats
- Class
- structural protein-RNA
- Method
- cryo-EM (4.08 Å)
- Summary
- Dmdcr-2-loqspd-slm1 in pre-dicing state
- Reference
-
Cao N, Wang J, Deng T, Fan B, Su S, Ma J, Wang HW (2025):
"Structural
basis of endo-siRNA processing by Drosophila Dicer-2 and
Loqs-PD." Nucleic Acids Res.,
53. doi: 10.1093/nar/gkaf102.
- Abstract
- Endogenous small interfering RNAs (endo-siRNAs or
esiRNAs) originate from either elongated endogenous
transcripts capable of forming complex fold-back structures
or from double-stranded regions generated through
intermolecular base pairing of convergently transcribed
mRNAs. The mechanism of maturation and functionality of
esiRNAs exhibit significant variation across diverse
species. In Drosophila melanogaster, esiRNAs reside in both
somatic and germline cells, where they serve as
post-transcriptional modulators for specific target RNAs.
Their maturation process critically relies on Dicer-2
(Dcr-2), with the assistance of its cofactor Loqs-PD. In
this study, we have successfully elucidated the cryo-EM
structures of Dcr-2/Loqs-PD complex bound to esiRNA
precursors (pre-esiRNAs) in various states. Our structural
and biochemical results reveal that ATP is essential for
the cleavage of esiRNAs by the Dcr-2/Loqs-PD complex, a
process analogous to the cleavage of double-stranded RNA
(dsRNA). When Loqs-PD is present, pre-esiRNAs are
preferentially loaded onto the Helicase domain of Dcr-2.
Moreover, as the Helicase domain exhibits a preference for
binding to the rigid end of double-stranded RNA, Dcr-2
tends to cleave pre-esiRNA from the small closed loop end,
rather than the loose and flexible open end.
