Non-coding RNA analysis — miRNAs (miRBase, miRDB targets), lncRNAs (LNCipedia, RNAcentral), circRNAs, snoRNAs, and other ncRNA classes. Distinct mechanisms per class — miRNAs repress mRNA; lncRNAs scaffold/decoy/enhance. Use for ncRNA function prediction, miRNA-target prediction, lncRNA functional annotation, and ncRNA-disease association queries.
Non-coding RNA analysis — miRNAs (miRBase, miRDB targets), lncRNAs (LNCipedia, RNAcentral), circRNAs, snoRNAs, and other ncRNA classes. Distinct mechanisms per class — miRNAs repress mRNA; lncRNAs scaffold/decoy/enhance. Use for ncRNA function prediction, miRNA-target prediction, lncRNA functional annotation, and ncRNA-disease association queries.
disable-model-invocation
true
Non-Coding RNA Analysis
Pipeline for identifying, annotating, and interpreting non-coding RNAs and their biological roles. Covers microRNAs (miRNAs), long non-coding RNAs (lncRNAs), and other ncRNA classes.
Key principles:
Class determines function — miRNAs repress mRNA translation; lncRNAs have diverse mechanisms (scaffolds, guides, decoys, enhancers); rRNAs/tRNAs are structural
Targets matter more than the ncRNA itself — for miRNAs, the regulated mRNA targets determine the phenotype
Expression context is critical — ncRNAs are highly tissue/cell-type specific
Conservation indicates function — deeply conserved ncRNAs (miR-let-7, MALAT1) have well-established roles
Type-based reasoning — look up, don't guess:
Non-coding RNA function depends on type: miRNA silences target mRNAs (look up targets in miRTarBase/TargetScan), lncRNA has diverse functions (scaffolding, guiding, decoying — check literature for the specific lncRNA), circRNA may sponge miRNAs.
For any ncRNA query: first identify the class from the name/sequence, then select the appropriate evidence source. Do not assume function based on name alone — a gene named "LINC" may have a characterized mechanism, or none at all. Always search PubMed for the specific ncRNA before interpreting. For miRNAs, validated targets (T1) from miRTarBase outweigh any computational prediction — a predicted target with no experimental support is a hypothesis, not a finding. For lncRNAs, mechanism is almost always determined by experimental studies; use with the lncRNA name + "mechanism" or "function" to find relevant evidence. For circRNAs, miRNA sponging is the most common proposed mechanism but is frequently over-claimed — look for CLIP-seq or reporter assay evidence before asserting it.
PubMed_search_articles
When to Use
"What are the targets of miR-21?"
"Find lncRNAs associated with breast cancer"
"Is this lncRNA conserved across species?"
"What miRNAs regulate TP53?"
"Annotate these non-coding RNA IDs"
"Which miRNAs are biomarkers for [disease]?"
Not this skill: For mRNA expression analysis, use tooluniverse-rnaseq-deseq2. For CRISPR screens, use tooluniverse-crispr-screen-analysis.
Core Tools
Tool
Use For
miRBase_search_mirna
Search miRNAs by name, accession, or sequence
miRBase_get_mirna
Detailed miRNA info (sequence, genomic location, family)
miRBase_get_mirna
Mature miRNA sequences and annotations
PubMed_search_articles
Search for validated miRNA targets in literature (e.g., "miR-21 target validation")
LNCipedia_search_lncrna
Search lncRNAs by name, gene symbol, or transcript ID
LNCipedia_get_lncrna
Detailed lncRNA transcript info (sequence, structure, conservation)
LNCipedia_get_lncrna_xrefs
lncRNA gene info with all transcript variants
LNCipedia_search_ncrna_by_type
List all transcripts for a lncRNA gene
LNCipedia_get_lncrna_publications
lncRNA sequence (FASTA format)
RNAcentral_search
Search all ncRNA types across databases
RNAcentral_get_by_accession
Detailed ncRNA annotations from 40+ databases
Rfam_get_family
RNA family details (structure, alignment, species distribution)
piRNA (26-31 nt, RNAcentral): Transposon silencing in germline
circRNA (variable, RNAcentral): miRNA sponges, protein scaffolds (experimental evidence required)
Identification workflow:
Name starts with miR- or hsa-mir- → search miRBase
Name starts with LINC, MALAT, HOTAIR, XIST, or ends in -AS1 → search LNCipedia
Any ncRNA type → search RNAcentral (aggregates all databases)
RNA family question → search Rfam
Phase 1: Target & Interaction Analysis
For miRNAs — the targets determine the biology:
PRIMARY TOOL: ENCORI_get_miRNA_targets looks up miRNA-target interactions from ENCORI/starBase (CLIP-seq-supported + computationally predicted), no download needed:
miRNA → targets: ENCORI_get_miRNA_targets(mirna="hsa-miR-21-5p", clip_min=1) — each hit reports clip_experiments (CLIP-seq support; higher = stronger experimental evidence) and predicted_by (which programs call it). Results are ranked by CLIP support, so the top rows are the best-supported targets.
gene → miRNAs: ENCORI_get_miRNA_targets(gene="TP53") — which miRNAs target a gene.
Supporting/fallback approaches:
3. Literature (for mechanism/validation context): PubMed_search_articles(query="miR-21 target validation luciferase")
4. Cross-references: miRBase_get_mirna_xrefs(accession="MIMAT0000076")
5. For novel miRNAs not in ENCORI: search PubMed for "[miRNA] target".
Well-studied miRNA targets (for common oncomiRs/tumor suppressors):
Prediction only (T3-T4): miRanda, PicTar, RNA22 — hypothesis generation only; do not report as findings
For lncRNAs — the mechanism varies:
lncRNA Mechanism
Example
How to Investigate
Chromatin modifier
HOTAIR, XIST
Check interacting proteins (PRC2, LSD1) via PubMed
Transcription regulator
NEAT1, MEG3
Check nearby genes (cis-regulation) via genomic location
miRNA sponge
MALAT1, circRNAs
Search for miRNA binding sites
Scaffold
NKILA, BCAR4
Check protein interactions
Enhancer RNA
eRNAs
Check ENCODE enhancer annotations
Phase 2: Expression & Tissue Specificity
GTEx_get_median_gene_expression(gene_symbol="MIR21") # miRNA host gene expression# Note: GTEx measures RNA-seq; miRNA expression may need miRNA-seq data from GEO
Interpretation: Tissue-restricted ncRNAs are often functionally important in that tissue. Ubiquitous ncRNAs (like MALAT1) tend to have housekeeping roles.
Interpretation: If miR-21 targets are enriched in apoptosis and PI3K-AKT signaling → miR-21 is an oncomiR that promotes survival by simultaneously suppressing multiple tumor suppressors.
miRTarBase has Cloudflare protection blocking programmatic access. Use the R/Bioconductor data package or bulk download:
# Option 1: Download from miRTarBase bulk export (requires browser download first)# Go to: https://mirtarbase.cuhk.edu.cn/~miRTarBase/miRTarBase_2025/# Download: hsa_MTI.xlsx (human miRNA-target interactions)# Option 2: Use the GitHub data dump# https://github.com/jorainer/mirtarbase — R package with cached data# Once you have the file:import pandas as pd
mti = pd.read_excel("hsa_MTI.xlsx") # or read_csv if TSV# Filter for your miRNA
mir21_targets = mti[mti['miRNA'].str.contains('hsa-miR-21', case=False, na=False)]
print(f"miR-21 validated targets: {len(mir21_targets)}")
# Filter by evidence strength
strong = mir21_targets[mir21_targets['Support Type'].str.contains(
'Luciferase|Reporter|Western|CLIP', case=False, na=False
)]
print(f" Strong evidence (reporter/CLIP): {len(strong)}")
for _, row in strong.head(10).iterrows():
print(f" {row['Target Gene']:10s} — {row['Support Type']}")
When download is not available: Use the built-in reference table in Phase 1 for well-studied miRNAs, or search PubMed for validated targets.
Limitations
miRNA target prediction is noisy — even the best algorithms have >50% false positive rates; always prioritize experimentally validated targets
lncRNA function is poorly characterized — only ~5% of annotated lncRNAs have known functions
Expression measurement varies — miRNA-seq, RNA-seq, and microarray capture different ncRNA classes; check the assay type
Species differences — miRNAs are often conserved but lncRNAs are frequently species-specific; cross-species lncRNA comparisons are unreliable
