| Citation (PMID preferred) | Evidence type | Supports/Refutes/Qualifies/Competing | Claim tested | Key finding | Organism/assay context | Confidence and limitations |
|---|---|---|---|---|---|---|
| Palavicini et al. 2009, RNA, PMID:19390115 | Direct assay + structural/evolutionary | Refutes | Does squid ADAR2 have tRNA-specific adenosine deaminase activity? | Cloned squid ADAR2 splice variants are homologs of vertebrate ADAR2, contain 2 or 3 dsRBDs plus deaminase domain, and recombinant proteins are active on duplex RNA; no tRNA substrate reported. sqADAR2a edits many sites in sqKv1.1A and sqKv1.2A transcripts. | Doryteuthis/Loligo opalescens; recombinant enzyme assays on K+ channel RNAs; nervous-system-derived transcripts. | Very high confidence for dsRNA-editing function because evidence is direct and species-specific; limitation: tests focused on mRNA/dsRNA substrates rather than explicitly excluding every possible tRNA activity. (pqac-00000001, pqac-00000002, pqac-00000013, pqac-00000014, pqac-00000015, pqac-00000017, pqac-00000020) |
| Hajji et al. 2022, RNA, doi:10.1261/rna.079266.122 | Review/database | Refutes | Is ADAR2 generally a tRNA deaminase? | Reviews ADAR2 as an enzyme that performs A-to-I editing in double-stranded RNA, especially site-selective recoding in mRNAs; places cephalopod editing within ADAR biology, not ADAT/tRNA editing. | Broad metazoan ADAR2 literature synthesis. | High confidence for family-level interpretation; limitation: not species-specific to Doryteuthis and not a primary assay. (pqac-00000000) |
| Fisher & Beal 2024, Mol Ther Nucleic Acids, doi:10.1016/j.omtn.2024.102284 | Structural/evolutionary review | Refutes | Does the catalytic machinery and substrate-recognition mode match tRNA deaminases or dsRNA ADARs? | ADAR2 active site uses zinc-coordinating His/Cys/Cys and catalytic Glu; base-flipping loop and dsRNA recognition define ADAR chemistry on duplex RNA. Distinguishes ADAR architecture from ADAT substrate systems. | Structural synthesis centered on human ADAR2 and related ADARs. | High confidence for mechanism; limitation: inferred to squid by homology, not direct squid structure. (pqac-00000010) |
| Ashley et al. 2024, Curr Issues Mol Biol, doi:10.3390/cimb46050243 | Structural/evolutionary review | Refutes | Is squid ADAR2 in the ADAT/tRNA-editing subfamily? | States ADARs possess dsRBDs and catalytic deaminase domain and act on dsRNA, whereas ADAT1 edits tRNA wobble positions and ADAT2/3 are distinct; conserved ADAR2 catalytic residues support ADAR-family assignment. | Comparative review across ADAR/ADAT proteins. | High confidence for subfamily distinction; limitation: review-level evidence rather than direct squid biochemistry. (pqac-00000004, pqac-00000005, pqac-00000011, pqac-00000012) |
| Budzko et al. 2023, Mol Ther Nucleic Acids, doi:10.1016/j.omtn.2023.102062 | Evolutionary review | Refutes | Could a generic adenosine-deaminase family label justify tRNA-specific annotation? | Describes ADAT as ancestral tRNA editor and ADARs as derived dsRNA editors that acquired dsRNA-binding domains; therefore ADAR and ADAT are sibling activities, not interchangeable. | Broad evolutionary synthesis of editing enzymes. | Moderate-high confidence for family history; limitation: not species-specific and not a primary experimental paper. (pqac-00000008) |
| Zhang et al. 2024, Cell & Bioscience, doi:10.1186/s13578-024-01216-6 | Review | Refutes | Are ADARs and ADATs functionally equivalent for GO annotation? | Explicitly distinguishes ADARs as acting on double-stranded RNA and ADATs as acting on tRNA, despite both catalyzing A-to-I conversion. | Broad review of RNA editing enzymes. | High confidence for substrate distinction; limitation: no direct squid assay. (pqac-00000009) |
| Erdmann et al. 2021, Crit Rev Biochem Mol Biol, doi:10.1080/10409238.2020.1856768 | Review | Refutes | Does squid ADAR2 have ADAR-like domain architecture expected for dsRNA editing? | Summarizes squid ADAR proteins as containing dsRBDs and C-terminal catalytic deaminase domains; dsRBD number affects dsRNA affinity. This architecture supports ADAR-like dsRNA editing, not ADAT-like tRNA editing. | Cross-species ADAR review including squid. | Moderate-high confidence; limitation: not direct activity assay and excerpt does not name every substrate. (pqac-00000003) |
| Colina et al. 2010, PLoS Biol, doi:10.1371/journal.pbio.1000540 | Direct functional assay | Refutes | Does squid nervous-system RNA editing involve ADAR-type mRNA recoding rather than tRNA editing? | Demonstrates functional consequences of RNA editing in squid Na+/K+-ATPase mRNA; notes human ADAR2 can edit squid sites except one, linking the phenomenon to ADAR-type mRNA editing on duplex structures. | Loligo opalescens specimen; edited transporter mRNA analyzed functionally. | High confidence that squid recoding is ADAR-style mRNA editing; limitation: assays center on substrate consequence more than direct enzyme purification from squid. (pqac-00000000) |
| Liscovitch-Brauer et al. 2017, Cell, doi:10.1016/j.cell.2017.03.025 | Comparative transcriptomics/evolutionary | Refutes | What class of RNA editing predominates in coleoid cephalopods? | Shows widespread transcriptome plasticity via A-to-I editing in cephalopods and notes squid ADAR2 splice variant with extra dsRBD; supports extensive ADAR-mediated recoding of transcripts, not tRNA-focused editing. | Cephalopod transcriptomes including squid neural tissues. | High confidence for biological context; limitation: does not biochemically assay tRNA substrates. (pqac-00000000) |
| Albertin et al. 2022, Nat Commun, doi:10.1038/s41467-022-29748-w | Genomics/transcriptomics | Qualifies | Is cephalopod editing pattern consistent with ADAR-mediated dsRNA editing? | Reports extensive A-to-I mRNA editing in cephalopods with nervous-system-enriched recoding and repetitive-element editing; notes ADAR2 editing patterns and relevance to Doryteuthis opalescens by comparison with congeneric squid. | Cephalopod genome/transcriptome analysis; Doryteuthis/Loligo comparative context. | High confidence for organismal context; limitation: not direct enzymology on C1JAR3. (pqac-00000000) |
| Rosenthal 2015, J Exp Biol, doi:10.1242/jeb.119065 | Review with functional synthesis | Refutes | What substrates are edited in squid and how does squid ADAR2 behave? | Describes extensive recoding in squid K+ channels and Na+/K+-ATPase and notes squid ADAR2 variants with extra dsRBMs edit more sites, reinforcing dsRNA/mRNA substrate specificity. | Functional overview of cephalopod RNA editing literature. | Moderate-high confidence; limitation: review rather than new primary assay. (pqac-00000016) |


*Table: This table summarizes primary and review evidence relevant to the annotation of Doryteuthis opalescens ADAR2. Across direct squid assays, structural comparisons, and recent reviews, the evidence consistently supports dsRNA-specific ADAR activity and refutes tRNA-specific adenosine deaminase activity.*