Regulation of KIR3DL3 Expression via miRNA

Rungtiwa Nutalai, Silvana Gaudieri, Amonrat Jumnainsong, Chanvit Leelayuwat

Research output: Contribution to journalArticle

Abstract

Killer-cell immunoglobulin-like receptor (KIR) 3DL3 is a framework gene present in all human KIR haplotypes. Although the structure of KIR3DL3 is suggestive of an inhibitory receptor, the function of KIR3DL3 has not been demonstrated and cognate ligands have not been identified. KIR3DL3 has been shown to be constitutively expressed at a low RNA level in peripheral blood mononuclear cell (PBMC) and decidual natural kill (NK) cells, but cell surface expression of KIR3DL3 cannot be detected. Accordingly, post-transcriptional regulation of KIR3DL3 should exist. Using bioinformatics analysis, we identified three candidate micro ribonucleic acids (miRNAs; miR-26a-5p, -26b-5p and -185-5p) that potentially regulate KIR3DL3 expression. Luciferase reporter assays utilizing constructs with mutated miRNA-binding sites of miR-26a-5p, -26b-5p and -185-5p in the 3'-untranslated region (3' UTR) of KIR3DL3 resulted in up-regulation of luciferase activity demonstrating a potential mechanism of gene regulation. Furthermore, knockdown of the same endogenous miRNAs using silencing ribonucleic acid (siRNA) led to induced surface expression of KIR3DL3. In conclusion, we provide a novel mechanism of functional regulation of KIR3DL3 via miRNAs. These findings are relevant in understanding the generation of KIR repertoire and NK cell clonality.

Original languageEnglish
Article number603
Number of pages11
JournalGenes
Volume10
Issue number8
DOIs
Publication statusPublished - Aug 2019

Cite this

Nutalai, R., Gaudieri, S., Jumnainsong, A., & Leelayuwat, C. (2019). Regulation of KIR3DL3 Expression via miRNA. Genes, 10(8), [603]. https://doi.org/10.3390/genes10080603
Nutalai, Rungtiwa ; Gaudieri, Silvana ; Jumnainsong, Amonrat ; Leelayuwat, Chanvit. / Regulation of KIR3DL3 Expression via miRNA. In: Genes. 2019 ; Vol. 10, No. 8.
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abstract = "Killer-cell immunoglobulin-like receptor (KIR) 3DL3 is a framework gene present in all human KIR haplotypes. Although the structure of KIR3DL3 is suggestive of an inhibitory receptor, the function of KIR3DL3 has not been demonstrated and cognate ligands have not been identified. KIR3DL3 has been shown to be constitutively expressed at a low RNA level in peripheral blood mononuclear cell (PBMC) and decidual natural kill (NK) cells, but cell surface expression of KIR3DL3 cannot be detected. Accordingly, post-transcriptional regulation of KIR3DL3 should exist. Using bioinformatics analysis, we identified three candidate micro ribonucleic acids (miRNAs; miR-26a-5p, -26b-5p and -185-5p) that potentially regulate KIR3DL3 expression. Luciferase reporter assays utilizing constructs with mutated miRNA-binding sites of miR-26a-5p, -26b-5p and -185-5p in the 3'-untranslated region (3' UTR) of KIR3DL3 resulted in up-regulation of luciferase activity demonstrating a potential mechanism of gene regulation. Furthermore, knockdown of the same endogenous miRNAs using silencing ribonucleic acid (siRNA) led to induced surface expression of KIR3DL3. In conclusion, we provide a novel mechanism of functional regulation of KIR3DL3 via miRNAs. These findings are relevant in understanding the generation of KIR repertoire and NK cell clonality.",
keywords = "killer-cell immunoglobulin-like receptor (KIR) 3DL3, miRNA, 3'untranslated region, post-transcriptional regulation, KILLER-CELL RECEPTOR, DNA METHYLATION, NK, KIR, MICRORNAS, ACTIVATION",
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Nutalai, R, Gaudieri, S, Jumnainsong, A & Leelayuwat, C 2019, 'Regulation of KIR3DL3 Expression via miRNA' Genes, vol. 10, no. 8, 603. https://doi.org/10.3390/genes10080603

Regulation of KIR3DL3 Expression via miRNA. / Nutalai, Rungtiwa; Gaudieri, Silvana; Jumnainsong, Amonrat; Leelayuwat, Chanvit.

In: Genes, Vol. 10, No. 8, 603, 08.2019.

Research output: Contribution to journalArticle

TY - JOUR

T1 - Regulation of KIR3DL3 Expression via miRNA

AU - Nutalai, Rungtiwa

AU - Gaudieri, Silvana

AU - Jumnainsong, Amonrat

AU - Leelayuwat, Chanvit

PY - 2019/8

Y1 - 2019/8

N2 - Killer-cell immunoglobulin-like receptor (KIR) 3DL3 is a framework gene present in all human KIR haplotypes. Although the structure of KIR3DL3 is suggestive of an inhibitory receptor, the function of KIR3DL3 has not been demonstrated and cognate ligands have not been identified. KIR3DL3 has been shown to be constitutively expressed at a low RNA level in peripheral blood mononuclear cell (PBMC) and decidual natural kill (NK) cells, but cell surface expression of KIR3DL3 cannot be detected. Accordingly, post-transcriptional regulation of KIR3DL3 should exist. Using bioinformatics analysis, we identified three candidate micro ribonucleic acids (miRNAs; miR-26a-5p, -26b-5p and -185-5p) that potentially regulate KIR3DL3 expression. Luciferase reporter assays utilizing constructs with mutated miRNA-binding sites of miR-26a-5p, -26b-5p and -185-5p in the 3'-untranslated region (3' UTR) of KIR3DL3 resulted in up-regulation of luciferase activity demonstrating a potential mechanism of gene regulation. Furthermore, knockdown of the same endogenous miRNAs using silencing ribonucleic acid (siRNA) led to induced surface expression of KIR3DL3. In conclusion, we provide a novel mechanism of functional regulation of KIR3DL3 via miRNAs. These findings are relevant in understanding the generation of KIR repertoire and NK cell clonality.

AB - Killer-cell immunoglobulin-like receptor (KIR) 3DL3 is a framework gene present in all human KIR haplotypes. Although the structure of KIR3DL3 is suggestive of an inhibitory receptor, the function of KIR3DL3 has not been demonstrated and cognate ligands have not been identified. KIR3DL3 has been shown to be constitutively expressed at a low RNA level in peripheral blood mononuclear cell (PBMC) and decidual natural kill (NK) cells, but cell surface expression of KIR3DL3 cannot be detected. Accordingly, post-transcriptional regulation of KIR3DL3 should exist. Using bioinformatics analysis, we identified three candidate micro ribonucleic acids (miRNAs; miR-26a-5p, -26b-5p and -185-5p) that potentially regulate KIR3DL3 expression. Luciferase reporter assays utilizing constructs with mutated miRNA-binding sites of miR-26a-5p, -26b-5p and -185-5p in the 3'-untranslated region (3' UTR) of KIR3DL3 resulted in up-regulation of luciferase activity demonstrating a potential mechanism of gene regulation. Furthermore, knockdown of the same endogenous miRNAs using silencing ribonucleic acid (siRNA) led to induced surface expression of KIR3DL3. In conclusion, we provide a novel mechanism of functional regulation of KIR3DL3 via miRNAs. These findings are relevant in understanding the generation of KIR repertoire and NK cell clonality.

KW - killer-cell immunoglobulin-like receptor (KIR) 3DL3

KW - miRNA

KW - 3'untranslated region

KW - post-transcriptional regulation

KW - KILLER-CELL RECEPTOR

KW - DNA METHYLATION

KW - NK

KW - KIR

KW - MICRORNAS

KW - ACTIVATION

U2 - 10.3390/genes10080603

DO - 10.3390/genes10080603

M3 - Article

VL - 10

JO - Genes

JF - Genes

SN - 2073-4425

IS - 8

M1 - 603

ER -

Nutalai R, Gaudieri S, Jumnainsong A, Leelayuwat C. Regulation of KIR3DL3 Expression via miRNA. Genes. 2019 Aug;10(8). 603. https://doi.org/10.3390/genes10080603