Loquacious is a double-stranded RNA-binding cofactor that helps Dicer enzymes produce regulatory small RNAs. The 464-residue PF isoform retains the three-domain architecture of the miRNA-processing PB isoform, supporting RNA recognition and association with Dcr-1 in cytoplasmic pre-miRNA processing. Other splice isoforms, especially PD, specialize in Dcr-2-dependent siRNA production. Small-RNA regulation connects loqs to development and germline stem-cell maintenance.
Summary: Double-stranded RNA binding is the supported specific molecular activity.
Reason: Double-stranded RNA binding is the supported specific molecular activity. Both RNA-binding DRBM domains are unchanged relative to characterized PB, so broad RNA binding can be replaced with GO:0003725.
ISS PMID:10908586 The drosophila melanogaster genome: translation factors and ...
ACCEPT
Summary: The ISS assignment is independently supported by biochemical dissection of PB and complete conservation of its two RNA-binding domains in PF.
Reason: The ISS assignment is independently supported by biochemical dissection of PB and complete conservation of its two RNA-binding domains in PF. RNA-binding specificity is established by these domains and substrate-binding experiments, not ARBA agreement.
IPI PMID:17666393 Functional anatomy of the Drosophila microRNA-generating enz...
KEEP AS NON CORE
Summary: Direct Dcr-1 association is mechanistically relevant and the interaction domain is retained in PF.
Reason: Direct Dcr-1 association is mechanistically relevant and the interaction domain is retained in PF. Generic protein binding adds little functional specificity, so preserve the IPI interaction as non-core and represent the RNA-processing role in the core synthesis.
Summary: The primary study describes predominantly cytoplasmic Loqs and cytoplasmic pre-miRNA processing.
Reason: The primary study describes predominantly cytoplasmic Loqs and cytoplasmic pre-miRNA processing. The nearly identical PF isoform retains the characterized processing architecture, making cytoplasmic localization a reasonable transfer independent of the electronic source.
IMP PMID:18634873 RAX is required for fly neuronal development and mouse embry...
KEEP AS NON CORE
Summary: The paper explicitly identifies dRax as loqs/R3D1 and reports a CNS axon phenotype in the fly mutant.
Reason: The paper explicitly identifies dRax as loqs/R3D1 and reports a CNS axon phenotype in the fly mutant. This gene-level developmental consequence is credible, while the direct evolved molecular role is small-RNA processing; the experiment does not isolate PF.
Mutant fly embryos homozygous for the insertion dRax[f00791] display highly abnormal commissural axon structure of the CNS
file:DROME/loqs/loqs-bioinformatics/RESULTS.md
All three annotated DRBM domains are fully retained.
GO:0009047 dosage compensation by hyperactivation of X chromosome
IGI PMID:22554892 A role for siRNA in X-chromosome dosage compensation in Dros...
UNDECIDED
Summary: The genetic interaction supports a gene-level siRNA connection to dosage compensation.
Reason: The genetic interaction supports a gene-level siRNA connection to dosage compensation. This record is specifically PB-like PF, whereas Dcr-2-associated PD supplies the established endo-siRNA mechanism. The paper does not resolve PF participation, so retain the annotation as undecided rather than rejecting a valid gene-level experiment.
We show that small interfering RNA (siRNA) mutations enhance the lethality of Drosophila males deficient in X recognition and partially rescue females that inappropriately dosage-compensate.
Summary: Regulation of gene expression follows directly from Loqs-assisted miRNA biogenesis and RNA silencing.
Reason: Regulation of gene expression follows directly from Loqs-assisted miRNA biogenesis and RNA silencing. This conclusion is independently grounded in primary experiments and conserved PF domains; the ARBA provenance of this row is not its biological justification.
IDA PMID:20037596 Loqs and R2D2 act sequentially in the siRNA pathway in Droso...
MODIFY
Summary: The supported specific step is pre-miRNA processing with Dcr-1.
Reason: The supported specific step is pre-miRNA processing with Dcr-1. The broad metabolism term can be replaced with GO:0031054; PF retains the PB RNA-binding and Dcr-1-association architecture.
IDA PMID:20037596 Loqs and R2D2 act sequentially in the siRNA pathway in Droso...
UNDECIDED
Summary: The cited experiments establish siRNA production by the loqs locus, with later isoform resolution assigning the Dcr-2 function to PD.
Reason: The cited experiments establish siRNA production by the loqs locus, with later isoform resolution assigning the Dcr-2 function to PD. X2J5X6 is PF and retains the third DRBM characteristic of PB rather than the PD-specific terminus. PF-specific siRNA-processing evidence is unavailable, so the exact-protein assignment remains unresolved; no claim of an erroneous gene-level experiment is made.
IMP PMID:18463630 The Drosophila hairpin RNA pathway generates endogenous shor...
UNDECIDED
Summary: The cited experiments establish siRNA production by the loqs locus, with later isoform resolution assigning the Dcr-2 function to PD.
Reason: The cited experiments establish siRNA production by the loqs locus, with later isoform resolution assigning the Dcr-2 function to PD. X2J5X6 is PF and retains the third DRBM characteristic of PB rather than the PD-specific terminus. PF-specific siRNA-processing evidence is unavailable, so the exact-protein assignment remains unresolved; no claim of an erroneous gene-level experiment is made.
IMP PMID:19644447 Endo-siRNAs depend on a new isoform of loquacious and target...
UNDECIDED
Summary: The cited experiments establish siRNA production by the loqs locus, with later isoform resolution assigning the Dcr-2 function to PD.
Reason: The cited experiments establish siRNA production by the loqs locus, with later isoform resolution assigning the Dcr-2 function to PD. X2J5X6 is PF and retains the third DRBM characteristic of PB rather than the PD-specific terminus. PF-specific siRNA-processing evidence is unavailable, so the exact-protein assignment remains unresolved; no claim of an erroneous gene-level experiment is made.
Endo-siRNA production depends on a specific Loqs isoform, Loqs-PD, which is distinct from the one, Loqs-PB, required for the production of microRNAs.
file:DROME/loqs/loqs-bioinformatics/RESULTS.md
All three annotated DRBM domains are fully retained.
GO:0030718 germ-line stem cell population maintenance
IMP PMID:17320391 The miRNA pathway intrinsically controls self-renewal of Dro...
KEEP AS NON CORE
Summary: The knockout/rescue study establishes an intrinsic germline stem-cell role for the PB-associated miRNA pathway.
Reason: The knockout/rescue study establishes an intrinsic germline stem-cell role for the PB-associated miRNA pathway. Conserved PF domain architecture supports a related contribution, but the developmental phenotype is downstream of the core RNA-processing activity and the study does not isolate PF.
IDA PMID:17666393 Functional anatomy of the Drosophila microRNA-generating enz...
ACCEPT
Summary: The preserved RNA-binding and Dcr-1-binding domains support the PB-like pre-miRNA-processing function of this PF isoform.
Reason: The preserved RNA-binding and Dcr-1-binding domains support the PB-like pre-miRNA-processing function of this PF isoform. The primary experiment concerns PB; transfer to PF is a sequence-supported inference, not a claim that PF itself was assayed.
IMP PMID:15918770 Normal microRNA maturation and germ-line stem cell maintenan...
ACCEPT
Summary: The preserved RNA-binding and Dcr-1-binding domains support the PB-like pre-miRNA-processing function of this PF isoform.
Reason: The preserved RNA-binding and Dcr-1-binding domains support the PB-like pre-miRNA-processing function of this PF isoform. The primary experiment concerns PB; transfer to PF is a sequence-supported inference, not a claim that PF itself was assayed.
IMP PMID:15985611 Dicer-1 and R3D1-L catalyze microRNA maturation in Drosophil...
ACCEPT
Summary: The preserved RNA-binding and Dcr-1-binding domains support the PB-like pre-miRNA-processing function of this PF isoform.
Reason: The preserved RNA-binding and Dcr-1-binding domains support the PB-like pre-miRNA-processing function of this PF isoform. The primary experiment concerns PB; transfer to PF is a sequence-supported inference, not a claim that PF itself was assayed.
IMP PMID:19644447 Endo-siRNAs depend on a new isoform of loquacious and target...
ACCEPT
Summary: The preserved RNA-binding and Dcr-1-binding domains support the PB-like pre-miRNA-processing function of this PF isoform.
Reason: The preserved RNA-binding and Dcr-1-binding domains support the PB-like pre-miRNA-processing function of this PF isoform. The primary experiment concerns PB; transfer to PF is a sequence-supported inference, not a claim that PF itself was assayed.
IMP PMID:17320391 The miRNA pathway intrinsically controls self-renewal of Dro...
KEEP AS NON CORE
Summary: The knockout/rescue study establishes an intrinsic germline stem-cell role for the PB-associated miRNA pathway.
Reason: The knockout/rescue study establishes an intrinsic germline stem-cell role for the PB-associated miRNA pathway. Conserved PF domain architecture supports a related contribution, but the developmental phenotype is downstream of the core RNA-processing activity and the study does not isolate PF.
Summary: The knockout/rescue study establishes an intrinsic germline stem-cell role for the PB-associated miRNA pathway.
Reason: The knockout/rescue study establishes an intrinsic germline stem-cell role for the PB-associated miRNA pathway. Conserved PF domain architecture supports a related contribution, but the developmental phenotype is downstream of the core RNA-processing activity and the study does not isolate PF.
Summary: Dcr-1/Loqs/AGO1 association during miRNA processing supports RISC-loading-complex membership through the PB-like mechanism.
Reason: Dcr-1/Loqs/AGO1 association during miRNA processing supports RISC-loading-complex membership through the PB-like mechanism. This is a mechanistic inference from primary complex experiments and retained PF domains, not validation by the ARBA label. It does not transfer the mammalian DICER1/TARBP2/AGO2 composition literally.
Loqs resides in a functional pre-miRNA processing complex
file:DROME/loqs/loqs-bioinformatics/RESULTS.md
All three annotated DRBM domains are fully retained.
GO:0070920 regulation of regulatory ncRNA processing
IDA PMID:21419681 Phosphate and R2D2 restrict the substrate specificity of Dic...
UNDECIDED
Summary: The paper examines Dcr-2 substrate specificity and distinguishes PD-associated siRNA processing from PB-associated miRNA processing.
Reason: The paper examines Dcr-2 substrate specificity and distinguishes PD-associated siRNA processing from PB-associated miRNA processing. A broad regulatory RNA-processing role is credible for PF, but the exact experimental activity and isoform underlying this row cannot be transferred uncritically from PD to PF. The annotation remains undecided at this accession while the independently supported pre-miRNA function is retained.
These computational predictions are reviewed separately from the GOA annotation set used for this review. The assessments below are from this project and do not constitute official GO annotations or endorsement by GO/UniProt. They are not included in the existing annotation review above.
Broad regulation of gene expression is supported by conserved miRNA-processing biology, but is less precise than the existing pre-miRNA-processing annotations.
Review rationale: Loqs-PF retains all three domains of the experimentally characterized PB miRNA-processing cofactor, differing by one linker-region lysine. Primary experiments demonstrate Loqs-dependent regulation of miRNA-target expression. Existing annotations include the more informative pre-miRNA-processing function, as well as the broad predicted term itself. LSP therefore reflects a correct but less precise description; ARBA agreement is not treated as validation. The mammalian pathway wording in the separate narrative prediction does not invalidate this broad GO claim.
Supporting Evidence:
PMID:15918769: "These results support a model in which Loquacious mediates miRNA biogenesis and, thereby, the expression of genes regulated by miRNAs."