RluA-1 is a nuclear RluA-family pseudouridine synthase expressed in Drosophila sensory neurons. Its conserved catalytic domain supports site-specific conversion of RNA uridine to pseudouridine, although the endogenous RNA substrates and modified positions remain unknown. RluA-1 restrains nociceptive sensitivity and influences sensory-neuron dendrite architecture.
Summary: The conserved catalytic mechanism establishes pseudouridine synthesis, but the particular RNA class and modification position are unresolved.
Reason: The conserved catalytic mechanism establishes pseudouridine synthesis, but the particular RNA class and modification position are unresolved. The primary comparison explicitly leaves substrate identification open, and RluA-family substrate recognition varies among characterized homologs. A target-specific RNA mapping result or a diagnostic substrate-specific subfamily placement is needed to distinguish rRNA from tRNA positions 31 or 32.
Each of the fully conserved non-catalytic residues (i.e., motif I, Figure 1A) and critical residues thought to be important for catalysis (asterisks, Figure 1A) are conserved in both RluA-1 and RluA-2.
Summary: RluA-1 has the conserved catalytic pseudouridine-synthase domain and active-site residues documented in the primary sequence/structure comparison.
Reason: RluA-1 has the conserved catalytic pseudouridine-synthase domain and active-site residues documented in the primary sequence/structure comparison. These features and the curated ancestral enzyme assignment strongly support uridine-to-pseudouridine isomerization. This is conserved enzymatic inference, while exact endogenous RNA targets remain unresolved.
Each of the fully conserved non-catalytic residues (i.e., motif I, Figure 1A) and critical residues thought to be important for catalysis (asterisks, Figure 1A) are conserved in both RluA-1 and RluA-2.
Summary: RNA interaction and modification are consistent with the conserved RluA-family enzyme.
Reason: RNA interaction and modification are consistent with the conserved RluA-family enzyme. Pseudouridine synthase activity or its corresponding synthesis process captures the molecular role more precisely than generic RNA binding, processing or modification.
Each of the fully conserved non-catalytic residues (i.e., motif I, Figure 1A) and critical residues thought to be important for catalysis (asterisks, Figure 1A) are conserved in both RluA-1 and RluA-2.
Summary: RNA interaction and modification are consistent with the conserved RluA-family enzyme.
Reason: RNA interaction and modification are consistent with the conserved RluA-family enzyme. Pseudouridine synthase activity or its corresponding synthesis process captures the molecular role more precisely than generic RNA binding, processing or modification.
Each of the fully conserved non-catalytic residues (i.e., motif I, Figure 1A) and critical residues thought to be important for catalysis (asterisks, Figure 1A) are conserved in both RluA-1 and RluA-2.
Summary: RNA interaction and modification are consistent with the conserved RluA-family enzyme.
Reason: RNA interaction and modification are consistent with the conserved RluA-family enzyme. Pseudouridine synthase activity or its corresponding synthesis process captures the molecular role more precisely than generic RNA binding, processing or modification.
Each of the fully conserved non-catalytic residues (i.e., motif I, Figure 1A) and critical residues thought to be important for catalysis (asterisks, Figure 1A) are conserved in both RluA-1 and RluA-2.
Summary: RluA-1 has the conserved catalytic pseudouridine-synthase domain and active-site residues documented in the primary sequence/structure comparison.
Reason: RluA-1 has the conserved catalytic pseudouridine-synthase domain and active-site residues documented in the primary sequence/structure comparison. These features and the curated ancestral enzyme assignment strongly support uridine-to-pseudouridine isomerization. This is conserved enzymatic inference, while exact endogenous RNA targets remain unresolved.
Each of the fully conserved non-catalytic residues (i.e., motif I, Figure 1A) and critical residues thought to be important for catalysis (asterisks, Figure 1A) are conserved in both RluA-1 and RluA-2.
Summary: RluA-1 has the conserved catalytic pseudouridine-synthase domain and active-site residues documented in the primary sequence/structure comparison.
Reason: RluA-1 has the conserved catalytic pseudouridine-synthase domain and active-site residues documented in the primary sequence/structure comparison. These features and the curated ancestral enzyme assignment strongly support uridine-to-pseudouridine isomerization. This is conserved enzymatic inference, while exact endogenous RNA targets remain unresolved.
Each of the fully conserved non-catalytic residues (i.e., motif I, Figure 1A) and critical residues thought to be important for catalysis (asterisks, Figure 1A) are conserved in both RluA-1 and RluA-2.
Summary: The conserved catalytic mechanism establishes pseudouridine synthesis, but the particular RNA class and modification position are unresolved.
Reason: The conserved catalytic mechanism establishes pseudouridine synthesis, but the particular RNA class and modification position are unresolved. The primary comparison explicitly leaves substrate identification open, and RluA-family substrate recognition varies among characterized homologs. A target-specific RNA mapping result or a diagnostic substrate-specific subfamily placement is needed to distinguish rRNA from tRNA positions 31 or 32.
Each of the fully conserved non-catalytic residues (i.e., motif I, Figure 1A) and critical residues thought to be important for catalysis (asterisks, Figure 1A) are conserved in both RluA-1 and RluA-2.
Summary: The conserved catalytic mechanism establishes pseudouridine synthesis, but the particular RNA class and modification position are unresolved.
Reason: The conserved catalytic mechanism establishes pseudouridine synthesis, but the particular RNA class and modification position are unresolved. The primary comparison explicitly leaves substrate identification open, and RluA-family substrate recognition varies among characterized homologs. A target-specific RNA mapping result or a diagnostic substrate-specific subfamily placement is needed to distinguish rRNA from tRNA positions 31 or 32.
Each of the fully conserved non-catalytic residues (i.e., motif I, Figure 1A) and critical residues thought to be important for catalysis (asterisks, Figure 1A) are conserved in both RluA-1 and RluA-2.
IDA PMID:33028630 Loss of Pseudouridine Synthases in the RluA Family Causes Hy...
NEW
Summary: A GFP exon trap directly localized RluA-1 protein to sensory-neuron nuclei. This is protein localization, distinct from membrane-tethered GFP used as a transcriptional reporter.
Reason: A GFP exon trap directly localized RluA-1 protein to sensory-neuron nuclei. This is protein localization, distinct from membrane-tethered GFP used as a transcriptional reporter.
a GFP exon trap for RluA-1 protein localized to the nuclei of these neurons.
GO:1904057 negative regulation of sensory perception of pain
IMP PMID:33028630 Loss of Pseudouridine Synthases in the RluA Family Causes Hy...
NEW
Summary: Loss of RluA-1 in nociceptors causes thermal and mechanical hyperalgesia, with null alleles and cDNA rescue supporting the locus assignment. RluA-1 therefore restrains nociceptive sensitivity; this does not identify the RNA target linking its enzymatic function to behavior.
Reason: Loss of RluA-1 in nociceptors causes thermal and mechanical hyperalgesia, with null alleles and cDNA rescue supporting the locus assignment. RluA-1 therefore restrains nociceptive sensitivity; this does not identify the RNA target linking its enzymatic function to behavior.
Tissue-specific RNAi, genetic null mutant, and cDNA rescue experiments all indicate that loss of the RluA-1 gene from whole animals, or specifically from nociceptors, results in hyperalgesia.
Core Functions
Catalyzes RNA pseudouridylation through the conserved stand-alone RluA-family mechanism; endogenous RNA targets are unresolved.
Each of the fully conserved non-catalytic residues (i.e., motif I, Figure 1A) and critical residues thought to be important for catalysis (asterisks, Figure 1A) are conserved in both RluA-1 and RluA-2.
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.
Pseudouridine synthesis is supported by target-resolved catalytic conservation and is already represented in the annotation record; precise RNA substrates remain unresolved.
Prediction method: ProtNLM2 · Version: UniProt API snapshot 2026-09-08
Review rationale: The pseudouridine-synthesis prediction is supported by the published alignment and structural comparison of the exact Q9VKV0 protein, including conserved catalytic residues. This supports the shared RluA-family reaction even though specific endogenous RNA targets have not been identified. The same process already occurs in the annotation record; its correctness is grounded in catalytic conservation rather than that overlap. More specific rRNA/tRNA substrate claims remain unresolved, so they are not used to label this prediction less precise.
Supporting Evidence:
PMID:33028630: "Each of the fully conserved non-catalytic residues (i.e., motif I, Figure 1A) and critical residues thought to be important for catalysis (asterisks, Figure 1A) are conserved in both RluA-1 and RluA-2."
PMID:33028630: "leaving to future investigation the nature of their substrates and whether they interact with RNA similarly as other synthases"