# Regulatory Potential of piRNAs Targeting Klotho and Other Genes

**Authors:** Anna Pyrkova, Kyrmyzy Akhmetova, Murat Zhanuzakov, Makpal Tauassarova, Aizhan Rakhmetulina, Raigul Niyazova, Saltanat Orazova, Piotr Zielenkiewicz, Anatoliy Ivashchenko

PMC · DOI: 10.3390/genes17020241 · Genes · 2026-02-18

## TL;DR

This study identifies piRNAs that may regulate the Klotho gene and other genes involved in metabolism and aging.

## Contribution

The paper computationally predicts novel piRNA–mRNA interactions involving the Klotho gene and other metabolic regulators.

## Key findings

- Several piRNAs were predicted to bind the Klotho (KL) mRNA in a single cluster of sites.
- piR-3215034 and piR-6885965 interact with mRNAs of multiple genes in different regions.
- Some piRNAs bind exclusively to the 3′UTR of FGF23 mRNA.

## Abstract

Background/Objectives: piRNAs (PIWI-interacting RNAs) can significantly modify the expression of protein-coding genes by suppressing the translation process. The aim of this work was to computationally evaluate the potential interactions between piRNAs and the mRNA of the Klotho gene, as well as other genes involved in key metabolic pathways related to health and lifespan regulation. Methods: Bioinformatic analysis was conducted using the MirTarget program, which determines the quantitative characteristics of predicted nucleotide interactions between piRNAs and mRNA targets. Results: Several piRNAs (piR-44682, piR-1940042, piR-3008660, piR-3215034, piR-6885965, and piR-7980636) were predicted to bind within a single cluster of binding sites on the KL mRNA. In addition, piR-6890096 was predicted to interact with the KL mRNA through full complementarity. The mRNAs of AFF2, BCL2L11, CPT1A, DAZAP1, NDRG3, SKIDA1, WBP4, ZIC5, and ZSWIM6 were predicted to interact with piR-3215034 and piR-6885965, forming clusters of binding sites located in the 5′ untranslated region (5′UTR), coding sequence (CDS), and 3′ untranslated region (3′UTR). Additionally, piR-576442, piR-1501557, piR-1845735, piR-2069834, and piR-3029987 were predicted to bind only within the 3′UTR of FGF23 mRNA. These results suggest that piRNAs are potential regulators of KL and other genes involved in key metabolic processes. Conclusions: The findings provide a basis for further experimental validation of predicted piRNA–mRNA interactions and their possible roles in gene regulation.

## Linked entities

- **Genes:** CG9701 (uncharacterized protein) [NCBI Gene 39872], KL (klotho) [NCBI Gene 9365], AFF2 (ALF transcription elongation factor 2) [NCBI Gene 2334], BCL2L11 (BCL2 like 11) [NCBI Gene 10018], CPT1A (carnitine palmitoyltransferase 1A) [NCBI Gene 1374], DAZAP1 (DAZ associated protein 1) [NCBI Gene 26528], NDRG3 (NDRG family member 3) [NCBI Gene 57446], SKIDA1 (SKI/DACH domain containing 1) [NCBI Gene 387640], WBP4 (WW domain binding protein 4) [NCBI Gene 11193], ZIC5 (Zic family zinc finger 5) [NCBI Gene 85416], ZSWIM6 (zinc finger SWIM-type containing 6) [NCBI Gene 57688], FGF23 (fibroblast growth factor 23) [NCBI Gene 8074]

## Full-text entities

- **Genes:** MIR200C (microRNA 200c) [NCBI Gene 406985] {aka MIRN200C, mir-200c}, SKIDA1 (SKI/DACH domain containing 1) [NCBI Gene 387640] {aka C10orf140, DLN-1}, CPT1A (carnitine palmitoyltransferase 1A) [NCBI Gene 1374] {aka CPT I, CPT1, CPT1-L, CPTI-L, L-CPT1}, CDS1 (CDP-diacylglycerol synthase 1) [NCBI Gene 1040] {aka CDS 1}, KCNN2 (potassium calcium-activated channel subfamily N member 2) [NCBI Gene 3781] {aka DYT34, KCa2.2, NEDMAB, SK2, SKCA2, SKCa 2}, WBP4 (WW domain binding protein 4) [NCBI Gene 11193] {aka FBP21, NEDHFDB}, NOTCH3 (notch receptor 3) [NCBI Gene 4854] {aka CADASIL, CADASIL1, CARASIL1, CASIL, FPLD1, IMF2}, MIR379 (microRNA 379) [NCBI Gene 494328] {aka MIRN379, hsa-mir-379, mir-379}, KLB (klotho beta) [NCBI Gene 152831] {aka BKL}, AFF2 (ALF transcription elongation factor 2) [NCBI Gene 2334] {aka FMR2, FMR2P, FRAXE, MRX2, OX19, XLID109}, FGF23 (fibroblast growth factor 23) [NCBI Gene 8074] {aka ADHR, FGFN, HFTC2, HPDR2, HYPF, PHPTC}, NDRG3 (NDRG family member 3) [NCBI Gene 57446], MIR339 (microRNA 339) [NCBI Gene 442907] {aka MIRN339, hsa-mir-339, mir-339}, MIR34A (microRNA 34a) [NCBI Gene 407040] {aka MIRN34A, miRNA34A, mir-34, mir-34a}, KL (klotho) [NCBI Gene 9365] {aka HFTC3, KLA}, RHOT1 (ras homolog family member T1) [NCBI Gene 55288] {aka ARHT1, MIRO-1, MIRO1}, ZIC5 (Zic family zinc finger 5) [NCBI Gene 85416], ZNF592 (zinc finger protein 592) [NCBI Gene 9640] {aka CAMOS, SCAR5}, BCL2L11 (BCL2 like 11) [NCBI Gene 10018] {aka BAM, BIM, BOD}, DAZAP1 (DAZ associated protein 1) [NCBI Gene 26528], ZSWIM6 (zinc finger SWIM-type containing 6) [NCBI Gene 57688] {aka AFND, NEDMAGA}, PIR (pirin) [NCBI Gene 8544]
- **Diseases:** diabetes (MESH:D003920), cancer (MESH:D009369), carcinomas of head and neck (MESH:D006258), schizophrenia (MESH:D012559), injury to (MESH:D014947), inflammatory (MESH:D007249), cardiovascular-renal-metabolic disorders (MESH:D024821), Parkinson's disease (MESH:D010300), pancreatic cancer (MESH:D010190), acute leukemia (MESH:D015470), squamous cell carcinoma (MESH:D002294), non-small cell lung cancer (MESH:D002289), obesity (MESH:D009765), cardiomyopathy (MESH:D009202), oncogenesis (MESH:D063646), diabetic nephropathy (MESH:D003928), hepatocellular carcinoma (MESH:D006528), malformations of the brain (MESH:D020785), and renal cell carcinoma (MESH:D002292), thoracic carcinoma (MESH:D013899), breast cancer (MESH:D001943), kidney diseases (MESH:D007674)
- **Chemicals:** nucleotide (MESH:D009711), phenylalanine (MESH:D010649), fatty acid (MESH:D005227)
- **Species:** Homo sapiens (human, species) [taxon 9606]
- **Mutations:** C1818T, G395A

## Full text

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## Figures

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## References

82 references — full list in the complete paper: https://tomesphere.com/paper/PMC12941268/full.md

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Source: https://tomesphere.com/paper/PMC12941268