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FB2026_01
,
released March 12, 2026
Dcr2, Dicer, dmDcr-2, dcr
DEAD/DEAH box helicase - mutants are defective in processing small interfering RNAs - has an RNA interference-independent function that modulates Toll immune signaling - produces 21-nt siRNAs with a remarkably high fidelity for efficient RNA silencing
Please see the JBrowse view of Dmel\Dcr-2 for information on other features
To submit a correction to a gene model please use the Contact FlyBase form
AlphaFold produces a per-residue confidence score (pLDDT) between 0 and 100. Some regions with low pLDDT may be unstructured in isolation.
Gene model reviewed during 5.44
Low-frequency RNA-Seq exon junction(s) not annotated.
Gene model reviewed during 5.50
None of the polypeptides share 100% sequence identity.
Component of the siRNA-directed RISC loading complex (siRLC), composed of at least Dcr-2, r2d2 and Taf11, which processes dsRNAs into duplex siRNAs which they then load onto AGO2 to initiate formation of the RNA-induced silencing complex (siRISC) (PubMed:21245036, PubMed:26257286, PubMed:35768503). The Dcr-2-r2d2 complex exists as a heterodimer and heterotetramer, with the latter showing higher siRNA binding activity (PubMed:26257286). Interacts (via N-terminus) with the siRISC loading cofactor r2d2; interaction is essential for formation of the siRLC and consequently, formation of the siRISC (PubMed:21245036, PubMed:21419681, PubMed:28416567, PubMed:35768503). Interacts with Taf11 (PubMed:26257286). Taf11 appears to form a tetramer which facilitates or stabilizes formation of the Dcr-2-r2d2 heterotetramer (PubMed:26257286). Interacts (via N-terminus) with dicing cofactor loqs isoform PD (loqs-PD) (via C-terminus); interaction is required for RNAi activity in producing siRNAs from a subset of endo- and exo-dsRNAs (PubMed:19635780, PubMed:21245036, PubMed:28874570, PubMed:29040648, PubMed:32843367, PubMed:35768513). In the absence of r2d2, may also be able to form an alternative siRLC with loqs-PD (PubMed:21245036). Interacts with wisp (via C-terminus) (PubMed:29317541). Able to interact with the other loqs isoforms (isoforms PA, PB and PC) (PubMed:19635780).
When in complex with loqs isoform PD (loqs-PD), undergoes significant conformational changes during the full ATP-dependent dicing reaction cycle for processing a 50 bp dsRNA with a 3' two-nucleotide overhang and a 5' monophosphate terminus (PubMed:35768513). At the initial dsRNA binding stage, the helicase and DUF283 domains transition from an extended to a closed conformation, this anchors the bound dsRNA through major and minor groove recognition and forms the ATP- and 5'-phosphate binding pockets required for dicing activity (PubMed:35768513). In the next ATP hydrolysis-driven steps, the dsRNAs is thread through the helicase domain towards the catalytic center (PubMed:35768513). The overall domain configuration is relatively rigid during the translocation process until the dsRNA terminus reaches the Platform-PAZ domains (PubMed:35768513). During the early-translocation stage, in which about 8 bp of the dsRNA duplex is threaded through the helicase domain towards the catalytic center, interactions between the DUF283 and RIIIDb domains prevent non-specific cleavage by blocking the access of dsRNA to the RNase active center (PubMed:35768513). In the mid-translocation stage, in which about 17 bp of the dsRNA duplex is thread towards the catalytic center, the dsRBD domain binds to the dsRNA, in the process bending and pushing the dsRNA towards the PAZ domain (PubMed:35768513). At the end of the translocation stage, around 21 bp of the dsRNA threads through the helicase domain into the PAZ-platform cassette, in the process disrupting the DUF283-RNaseIIIb interaction, allowing the dsRNA substrate to enter the catalytic active center of the RIIID domains for precise cleavage, and thus achieves the fully active dicing conformation (PubMed:35768513). In this structure, a clear breakage of the dsRNA after the dicing near to the catalytic center occurs exactly 21 bp away from the PAZ-domain-binding terminus (PubMed:35768513). During the post-dicing state, the cleaved siRNA is released, and the remaining dsRNA duplex bound by the helicase domain returns to a conformation similar to the early-translocation state, which enables the complex to start the next dicing cycle (PubMed:35768513).
The N-terminal helicase domain, containing the Helicase ATP-binding, Helicase C-terminal and Helicase insertion domains, functions in dsRNA stimulated ATPase activity and RNA translocation during the dicing reaction (PubMed:15066283, PubMed:21419681, PubMed:35768503, PubMed:35768513). Essential for processing endogenous and viral dsRNAs (PubMed:24009507, PubMed:28416567, PubMed:32843367). Binds and hydrolyzes ATP enabling the dicer to translocate along the long dsRNA substrates, and produce siRNAs processively from the end (PubMed:21419681, PubMed:29269422). Some reports suggest the domain is essential for the recognition and initial binding of both blunt (BLT) and 3' overhanging (3'ovr) termini dsRNA substrates (PubMed:35768503, PubMed:35768513). However, another reports found that the helicase domain is only required for binding and correct cleavage of BLT dsRNAs and is dispensable for processing of 3'ovr termini dsRNAs (PubMed:29269422, PubMed:32843367). One of the reports suggest that the helicase domain recognizes dsRNA with BLT termini, and then initiates processive cleavage via a threading mechanism in which the BLT dsRNA is locally unwound and threaded through the helicase domain in an ATP-dependent manner (PubMed:29269422).
The PAZ and platform domain is important for ensuring length fidelity of siRNAs, substrate discrimination, cleavage and anchoring of 3' overhanging (3'ovr) termini substrates, and the positive regulation of Tl (PubMed:26601278, PubMed:27872309, PubMed:29269422, PubMed:35768503). The platform-PAZ domains are important for mediating the ATP-independent cleavage of dsRNAs with 3' overhanging (3'ovr) dsRNAs into 22mer siRNAs (PubMed:29269422). Substrate dsRNAs with blunt termini, are threaded through the helicase domain, cleaved and then the 2-nt 3' overhang of the dsRNA is recognized and anchored by the 5'-pocket in the platform-PAZ domain (PubMed:29269422). The PAZ domain recognizes and anchors the 5'-monophosphate of long dsRNA substrates, positioning the substrate so that the RNase III domain can cleave the dsRNAs 21 nt away from their 5' end (PubMed:27872309, PubMed:35768503). Although it is important for ensuring length fidelity of 21-nt siRNA production, it is not required for efficient siRNA production (PubMed:27872309, PubMed:35768503). Important for substrate discrimination (PubMed:24488111, PubMed:29550490). Inorganic phosphate appears to occupy the same binding pocket in the PAZ domain as the 5' monophosphorylated end of short dsRNAs, pre-miRNAs or hairpin RNA substrates, and so once bound, the inorganic phosphate likely blocks binding and thus cleavage of the dsRNAs (PubMed:24488111, PubMed:29550490). Physiological concentrations of inorganic phosphate inhibit processing of the inappropriate substrates microRNAs (pre-miRNAs) and short dsRNAs, whereas cleavage of long dsRNAs is not inhibited possibly because they are recognized by a different domain/s i.e. the helicase domain and/or the central dsRNA binding domain (PubMed:21419681, PubMed:24488111, PubMed:29550490). This suggests that binding to inorganic phosphate may block binding to nonphysiological substrates, such as pre-miRNAs function to prevent the enzyme from processing nonphysiological dsRNAs substrates (PubMed:21419681, PubMed:24488111, PubMed:29550490). This domain is also important for the ATP-dependent cleavage reaction (PubMed:32843367). The PAZ domain also interacts with the Tl mRNA 3'UTR, and is therefore important for the positive regulation of Tl at the post-transcriptional level, and thus mediating Toll signaling (PubMed:26601278).
The DRBM domain or RNA binding domain (RBD), is important for efficient and high-fidelity production of 21 nucleotide siRNAs, and siRNA loading onto AGO2.
Interactions between the DUF283 and RIIIDb domains prevent non-specific cleavage by blocking the access of dsRNA to the RNase active center.
Click to get a list of regulatory features (enhancers, TFBS, etc.) and gene disruptions (point mutations, indels, etc.) within or overlapping Dmel\Dcr-2 using the Feature Mapper tool.
The testis specificity index was calculated from modENCODE tissue expression data by Vedelek et al., 2018 to indicate the degree of testis enrichment compared to other tissues. Scores range from -2.52 (underrepresented) to 5.2 (very high testis bias).
JBrowse - Visual display of RNA-Seq signals
View Dmel\Dcr-2 in JBrowse2-83
2-86.2
Please Note FlyBase no longer curates genomic clone accessions so this list may not be complete
Please Note This section lists cDNAs and ESTs that fall within the genomic extent of the gene model, which may include cDNAs and ESTs of genes within introns, or of overlapping genes. Please see JBrowse for alignment of the cDNAs and ESTs to the gene model.
For each fully sequenced cDNA the DGRC maintains various forms of the cDNA (e.g tagged or untagged) in several different host vectors for subsequent cloning and expression in Drosophila and Drosophila cell lines.
polyclonal
monoclonal
Dcr-2 is required for maintenance of long-distance chromosomal interactions between endogenous PcG target loci.
Dcr-2 is in the top 2% of fastest-evolving Drosophila genes.
Expression is enriched in embryonic gonads.
Dcr-2 is not required for repeat-associated small interfering RNA (rasiRNA) production
The orientation of the Dcr-2/r2d2 protein heterodimer on the siRNA duplex determines which siRNA strand associates with the core RISC (RNA-induced silencing complex) protein AGO2. r2d2 protein binds the siRNA end with the greatest double-stranded character, thereby orienting the Dcr-2/r2d2 heterodimer on the siRNA duplex. Strong binding by the r2d2 protein requires a 5'-phosphate on the siRNA strand that is excluded from the RISC.
Dcr-2 protein alone efficiently cleaves dsRNA into siRNA. This enzymatic activity is not affected by association with r2d2 protein. Dcr-2 protein alone does not bind siRNA, but the r2d2/Dcr-2 protein complex binds siRNA and also facilitates the loading of siRNA onto the RNA-initiated silencing complex (RISC). This latter activity is dependent on the dsRNA-binding domains of the r2d2 protein.
Source for identity of: Dcr-2 CG6493
