Mir26a-1 is one of two mouse loci encoding the mir-26a precursor, embedded in an intron of a CTDSP-family host gene. The mature miR-26a is a guide RNA that directs Argonaute/RISC to complementary sites in target mRNA 3' UTRs. Two specific roles are well supported: repression of the RSK3 kinase in hippocampal neurons, where miR-26a is required for the maintenance phase of long-term potentiation and for dendritic spine enlargement; and cooperation with its CTDSP host genes to hypophosphorylate pRb and block the G1/S transition. miR-26a is also abundant in extracellular vesicles and appears in many circulating-miRNA biomarker surveys, which is a property of its abundance rather than a separate function.
| GO Term | Evidence | Action | Reason |
|---|---|---|---|
| GO:0016442 RISC complex | IEA GO_REF:0000115 | ACCEPT | Summary: Rfam2GO annotation placing the mature miRNA in RISC. Reason: Mature miR-26a is loaded into Argonaute/RISC; this is core to how the gene product works. |
| GO:0035195 miRNA-mediated post-transcriptional gene silencing | IEA GO_REF:0000115 | ACCEPT | Summary: Rfam2GO annotation of the generic microRNA process. Reason: Correct and core for a mir-26a precursor. |
| GO:0035195 miRNA-mediated post-transcriptional gene silencing | IDA PMID:22210897 MicroRNA-26a/b and their host genes cooperate to inhibit the... | ACCEPT | Summary: Direct-assay support for miR-26a-mediated target repression. Reason: Gain- and loss-of-function experiments show miR-26a directly suppresses targets to lower ppRb, which is post-transcriptional silencing by the mature miRNA. Supporting Evidence: PMID:22210897 Gain- and loss-of-function studies showed that miR-26a/b and CTDSP1/2/L synergistically decreased the phosphorylated form of pRb (ppRb), and blocked G1/S-phase progression |
| GO:0016442 RISC complex | IDA PMID:24205035 Profiling circulating microRNA expression in experimental se... | ACCEPT | Summary: Argonaute 2 immunoprecipitation places circulating miR-26a in RISC. Reason: Unlike the two process rows from this paper, the RISC row rests on a direct biochemical assay - Ago2 immunoprecipitation recovering miR-26a - and is correct. Supporting Evidence: PMID:24205035 Immunoprecipitation with the Argonaute 2 ribonucleoprotein complex revealed significantly increased expression of the 10 miRNA targets in the serum of mice after CLP |
| GO:0009617 response to bacterium | IEP PMID:24205035 Profiling circulating microRNA expression in experimental se... | REMOVE | Summary: Contradicted by the source paper's own control experiment, which excludes bacterium-sensing pathways as the cause of the expression change. Reason: This is a circulating-biomarker survey: miR-26a rises in whole blood and serum after cecal ligation and puncture. The authors then asked whether bacterial sensing drives that rise and concluded it does not - the increase persists in Tlr2, Tlr4 and NF-kB knockouts. Annotating miR-26a as acting upstream of or within "response to bacterium" therefore asserts exactly what the cited paper tested and rejected. This is not a marginal over-annotation but a claim the source contradicts, which is the bar for REMOVE. It is also one of 58 IEP rows to this term from this single paper. Supporting Evidence: PMID:24205035 which indicated that the transcription of these miRNAs was not directly mediated by the TLR2/NF-ΞΊB or TLR4/NF-ΞΊB pathway, and pathways induced by exposure to the gram-positive or gram-negative bacteria |
| GO:0009611 response to wounding | IEP PMID:24205035 Profiling circulating microRNA expression in experimental se... | MARK AS OVER ANNOTATED | Summary: Reflects the surgical sepsis procedure used to perturb the animals, not a function of miR-26a in wound responses. Reason: Cecal ligation and puncture is a surgical injury, so "response to wounding" describes the experimental manipulation rather than anything shown about miR-26a. The measured quantity is the level of a miRNA circulating in blood and serum - a biomarker readout - and no experiment places miR-26a upstream of or within a wound response. Retained as over-annotated rather than removed because, unlike the bacterium row, the paper does not actively argue against it. Supporting Evidence: PMID:24205035 these miRNA targets were significantly up-regulated in the whole blood and serum but not in the WBCs |
| GO:0070062 extracellular exosome | IDA PMID:24205035 Profiling circulating microRNA expression in experimental se... | KEEP AS NON CORE | Summary: Direct measurement of miR-26a in isolated exosomes. Reason: Supported by direct assay - miR-26a is one of six miRNAs significantly enriched in exosomes isolated from serum. Kept as non-core because extracellular vesicle packaging is a distribution property of an abundant miRNA rather than the activity that defines mir-26a. Supporting Evidence: PMID:24205035 the levels of 6 (miR-16, miR-17, miR-20a, miR-20b, miR-26a, and miR-26b) of these 10 miRNA targets increased significantly in exosomes |
| GO:0060291 long-term synaptic potentiation | IEP PMID:25858512 miR-26a and miR-384-5p are required for LTP maintenance and ... | ACCEPT | Summary: Correct and core; the source paper establishes it functionally rather than by expression alone. Reason: miR-26a is one of the two title miRNAs of this study, shown to be required for the maintenance phase of LTP and for spine enlargement through repression of RSK3, with a 3' UTR reporter confirming the target. Together with the mir-384 row this is the positive control for the paper's 130-member IEP batch: the term is defensible here because the miRNA was perturbed and the phenotype measured, which is not true of most of the cohort. The IEP code understates the evidence, which is IMP-grade. Supporting Evidence: PMID:25858512 we demonstrate that miR-26a and miR-384-5p specifically affect the maintenance, but not induction, of LTP and different stages of spine enlargement by regulating the expression of RSK3 |
| GO:0003730 mRNA 3'-UTR binding | IDA PMID:25858512 miR-26a and miR-384-5p are required for LTP maintenance and ... | NEW | Summary: Added so the core molecular function is represented in the annotation block. Reporter assays show miR-26a acts through binding sites in the RSK3 3' UTR. Reason: GOA carries no molecular function for mir-26a. The LTP study tested RSK3 as a direct target with mCherry reporters carrying the RSK3 3' UTR binding-site sequences, supporting mRNA 3'-UTR binding as the mature miRNA's activity. Supporting Evidence: PMID:25858512 We generated miR-26a and miR-384-5p reporter constructs by inserting the sequences surrounding their predicted binding sites in the 3β² UTR of RSK3 behind the destabilized mCherry gene |
| GO:0071260 cellular response to mechanical stimulus | IDA PMID:25959411 MiR-154-5p regulates osteogenic differentiation of adipose-d... | UNDECIDED | Summary: Cannot be adjudicated from the cached record. Reason: The cached publication is abstract-only and the abstract concerns miR-154-5p and Wnt11 in tensile-stressed mesenchymal stem cells, with no mention of miR-26. The curator who made this IDA will have read the full text, which may well assay miR-26a alongside the title miRNA, so this is left undecided pending full-text access rather than challenged. |
| GO:0001933 negative regulation of protein phosphorylation | IDA PMID:22210897 MicroRNA-26a/b and their host genes cooperate to inhibit the... | KEEP AS NON CORE | Summary: Reduction of phosphorylated pRb by miR-26a/b with their host genes. Reason: Well supported - miR-26a lowers ppRb levels. Kept as non-core because it is a downstream consequence of miR-26a-directed target repression rather than a distinct activity of the miRNA. Supporting Evidence: PMID:22210897 Gain- and loss-of-function studies showed that miR-26a/b and CTDSP1/2/L synergistically decreased the phosphorylated form of pRb (ppRb), and blocked G1/S-phase progression |
| GO:2000134 negative regulation of G1/S transition of mitotic cell cycle | IDA PMID:22210897 MicroRNA-26a/b and their host genes cooperate to inhibit the... | ACCEPT | Summary: Direct functional evidence that miR-26a blocks G1/S progression. Reason: Gain- and loss-of-function experiments in primary fibroblasts and regenerating liver show miR-26a/b block G1/S-phase progression via pRb, an established specific role distinct from the generic miRNA process. Supporting Evidence: PMID:22210897 Gain- and loss-of-function studies showed that miR-26a/b and CTDSP1/2/L synergistically decreased the phosphorylated form of pRb (ppRb), and blocked G1/S-phase progression |
| GO:0071222 cellular response to lipopolysaccharide | IDA PMID:18762567 miR-181b negatively regulates activation-induced cytidine de... | UNDECIDED | Summary: Cannot be adjudicated; the cited paper is about a different miRNA in the cached text. Reason: PMC full text is cached for this reference and contains no mention of miR-26; the paper is about miR-181b regulating AID in B cells. Because the cached full text may be incomplete and the curator saw the published figures, this is left undecided for a curator to confirm rather than removed. |
| GO:0007566 embryo implantation | IDA PMID:18556655 MicroRNA expression and regulation in mouse uterus during em... | UNDECIDED | Summary: Cannot be adjudicated from the cached record; likely expression-based. Reason: The cached record is abstract-only and does not mention miR-26. The title describes an expression survey of the mouse uterus during implantation, so the underlying data may be an expression pattern, in which case the row would raise the same agency question as the other expression-derived annotations here. Left undecided pending full text. |
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Download this section (compressed HTML)Q: Do the two mouse loci Mir26a-1 and Mir26a-2 contribute differently to the LTP and cell-cycle roles, given their distinct CTDSP host genes?
Suggested experts: microRNA biologists, mouse geneticists
Q: Is the rise of circulating miR-26a in sepsis models a passive consequence of tissue damage, given that it survives loss of TLR2, TLR4 and NF-kB?
Suggested experts: sepsis researchers, extracellular vesicle biologists
Experiment: Locus-specific deletion of Mir26a-1 versus Mir26a-2 followed by hippocampal LTP recording
Hypothesis: The two loci are partially redundant for LTP maintenance, with the dominant contribution from the more highly expressed locus in CA1
Type: mouse genetics
Experiment: Ago HITS-CLIP in CA1 before and after LTP induction in wild-type and Mir26a-null slices
Hypothesis: RSK3 is one of a small set of miR-26a-dependent Argonaute targets that change occupancy during LTP maintenance
Type: high-throughput sequencing
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