# miRNA regulation in brain tissue space: the 3′UTR perspective

**Authors:** Denise Aigner, Florian Bartsch, Poojashree Bhaskar, Lisa Emmenegger, Nikos Karaiskos, Nikolaus Rajewsky, Agnieszka Rybak-Wolf

PMC · DOI: 10.1261/rna.080850.125 · RNA · 2026-04-01

## TL;DR

This review explores how miRNAs and 3′UTRs regulate gene expression in brain tissue and highlights the need for better tools to study them spatially.

## Contribution

The paper introduces a focus on the spatial regulation of miRNAs and 3′UTRs in neurodevelopment and neuronal function.

## Key findings

- Current methods cannot simultaneously quantify miRNAs and their target 3′UTRs in space.
- 3′UTR isoform variation in spatial contexts remains largely unexplored.
- The paper proposes future strategies for studying miRNA and 3′UTR regulation in brain tissue.

## Abstract

MicroRNAs (miRNAs) are key regulators of gene expression in both health and disease. Their expression and regulatory functions are highly complex and spatiotemporally organized within tissues. In recent years, spatial transcriptomics has made significant progress in quantifying RNA expression at subcellular resolution in tissue sections. However, no current method can quantify miRNAs and their target 3′ untranslated regions (3′UTRs) in space simultaneously. Furthermore, although 3′UTRs harbor critical miRNA target sites, 3′UTR isoform variation in space is largely unexplored. In this review, we discuss the role of miRNA-mediated regulation. We focus on neurodevelopment and neuronal function, where miRNAs and 3′UTRs have particularly complex and important functions. We summarize current experimental and computational approaches for spatial quantification of miRNAs and 3′UTRs, highlight existing challenges, and propose strategies for future research.

## Full-text entities

- **Genes:** let-7 (ncRNA) [NCBI Gene 266952], PTEN (phosphatase and tensin homolog) [NCBI Gene 5728] {aka 10q23del, BZS, CWS1, DEC, GLM2, MHAM}, lsy-6 (ncRNA) [NCBI Gene 3565492], act-5 (Actin) [NCBI Gene 176793], mir-124 (ncRNA) [NCBI Gene 3565990], lin-28 (Protein lin-28) [NCBI Gene 172626], ENPEP (glutamyl aminopeptidase) [NCBI Gene 2028] {aka APA, CD249, gp160}, lin-41 (Protein lin-41) [NCBI Gene 172760], LILRB1 (leukocyte immunoglobulin like receptor B1) [NCBI Gene 10859] {aka CD85J, ILT-2, ILT2, LIR-1, LIR1, MIR-7}, apl-1 (Amyloid-beta-like protein) [NCBI Gene 180783], drosha (drosha ribonuclease III) [NCBI Gene 567505] {aka im:7150667, rnasen, zgc:158612}, sox-2 (HMG box domain-containing protein;Transcription factor sox-2) [NCBI Gene 181002]
- **Diseases:** Alzheimer's disease (MESH:D000544), seizures (MESH:D012640), embryonic lethality (MESH:D020964), STEMNESS (MESH:D020295), PAS (MESH:D009371), cancer (MESH:D009369), cortical malformations (MESH:D054220), Parkinson's disease (MESH:D010300), SYSTEMS (MESH:D015619), pain (MESH:D010146), neurodegenerative diseases (MESH:D019636), developmental defects (MESH:D000094602), motor neuron disorders (MESH:D016472), autism (MESH:D001321), epilepsy (MESH:D004827)
- **Chemicals:** paraffin (MESH:D010232), formalin (MESH:D005557), poly(A) (MESH:D011061), 4-thiouridine (MESH:D013891)
- **Species:** Homo sapiens (human, species) [taxon 9606], C. elegans [taxon 328850], Mus musculus (house mouse, species) [taxon 10090], Caenorhabditis elegans (species) [taxon 6239], Danio rerio (leopard danio, species) [taxon 7955]

## Full text

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## Figures

2 figures with captions in the complete paper: https://tomesphere.com/paper/PMC12990811/full.md

## References

210 references — full list in the complete paper: https://tomesphere.com/paper/PMC12990811/full.md

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Source: https://tomesphere.com/paper/PMC12990811