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Exonized Alu repeats in the 3’UTR of a CYP20A1_Alu-LT transcript act as a miRNA sponge

OBJECTIVE: Alu repeats have gained huge importance in the creation and modification of regulatory networks. We previously reported a unique isoform of human CYP20A1 i.e. CYP20A1_Alu-LT with 23 Alu repeats exonized in its 9 kb long 3’UTR with 4742 potential binding sites for 994 miRNAs. The role of t...

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Autores principales: Singhal, Khushboo, Dhamija, Sonam, Mukerji, Mitali
Formato: Online Artículo Texto
Lenguaje:English
Publicado: BioMed Central 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9996890/
https://www.ncbi.nlm.nih.gov/pubmed/36895043
http://dx.doi.org/10.1186/s13104-023-06289-z
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author Singhal, Khushboo
Dhamija, Sonam
Mukerji, Mitali
author_facet Singhal, Khushboo
Dhamija, Sonam
Mukerji, Mitali
author_sort Singhal, Khushboo
collection PubMed
description OBJECTIVE: Alu repeats have gained huge importance in the creation and modification of regulatory networks. We previously reported a unique isoform of human CYP20A1 i.e. CYP20A1_Alu-LT with 23 Alu repeats exonized in its 9 kb long 3’UTR with 4742 potential binding sites for 994 miRNAs. The role of this transcript was hypothesized as a potential miRNA sponge in primary neurons as its expression correlated with that of 380 genes having shared miRNA sites and enriched in neuro-coagulopathy. This study provides experimental evidence for the miRNA sponge activity of CYP20A1_Alu-LT in neuronal cell lines. RESULTS: We studied the Alu-rich fragment of the CYP20A1_Alu-LT extended 3’UTR with > 10 binding sites for miR-619-5p and miR-3677-3p. Enrichment of the Alu-rich fragment with Ago2 confirmed miRNA association of this transcript. Cloning the fragment downstream of a reporter gene led to a 90% decrease in luciferase activity. Overexpression and knockdown studies revealed a positive correlation between the expression of CYP20A1_Alu-LT and miR-619-5p / miR-3677-3p target genes. GAP43, one of the key modulators of nerve regeneration, was significantly altered by the expression of CYP20A1_Alu-LT. This study, for the first time, provides evidence for a unique regulatory function of exonized Alu repeats as miRNA sponges. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s13104-023-06289-z.
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spelling pubmed-99968902023-03-10 Exonized Alu repeats in the 3’UTR of a CYP20A1_Alu-LT transcript act as a miRNA sponge Singhal, Khushboo Dhamija, Sonam Mukerji, Mitali BMC Res Notes Research Note OBJECTIVE: Alu repeats have gained huge importance in the creation and modification of regulatory networks. We previously reported a unique isoform of human CYP20A1 i.e. CYP20A1_Alu-LT with 23 Alu repeats exonized in its 9 kb long 3’UTR with 4742 potential binding sites for 994 miRNAs. The role of this transcript was hypothesized as a potential miRNA sponge in primary neurons as its expression correlated with that of 380 genes having shared miRNA sites and enriched in neuro-coagulopathy. This study provides experimental evidence for the miRNA sponge activity of CYP20A1_Alu-LT in neuronal cell lines. RESULTS: We studied the Alu-rich fragment of the CYP20A1_Alu-LT extended 3’UTR with > 10 binding sites for miR-619-5p and miR-3677-3p. Enrichment of the Alu-rich fragment with Ago2 confirmed miRNA association of this transcript. Cloning the fragment downstream of a reporter gene led to a 90% decrease in luciferase activity. Overexpression and knockdown studies revealed a positive correlation between the expression of CYP20A1_Alu-LT and miR-619-5p / miR-3677-3p target genes. GAP43, one of the key modulators of nerve regeneration, was significantly altered by the expression of CYP20A1_Alu-LT. This study, for the first time, provides evidence for a unique regulatory function of exonized Alu repeats as miRNA sponges. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s13104-023-06289-z. BioMed Central 2023-03-09 /pmc/articles/PMC9996890/ /pubmed/36895043 http://dx.doi.org/10.1186/s13104-023-06289-z Text en © The Author(s) 2023 https://creativecommons.org/licenses/by/4.0/Open AccessThis article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) . The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/ (https://creativecommons.org/publicdomain/zero/1.0/) ) applies to the data made available in this article, unless otherwise stated in a credit line to the data.
spellingShingle Research Note
Singhal, Khushboo
Dhamija, Sonam
Mukerji, Mitali
Exonized Alu repeats in the 3’UTR of a CYP20A1_Alu-LT transcript act as a miRNA sponge
title Exonized Alu repeats in the 3’UTR of a CYP20A1_Alu-LT transcript act as a miRNA sponge
title_full Exonized Alu repeats in the 3’UTR of a CYP20A1_Alu-LT transcript act as a miRNA sponge
title_fullStr Exonized Alu repeats in the 3’UTR of a CYP20A1_Alu-LT transcript act as a miRNA sponge
title_full_unstemmed Exonized Alu repeats in the 3’UTR of a CYP20A1_Alu-LT transcript act as a miRNA sponge
title_short Exonized Alu repeats in the 3’UTR of a CYP20A1_Alu-LT transcript act as a miRNA sponge
title_sort exonized alu repeats in the 3’utr of a cyp20a1_alu-lt transcript act as a mirna sponge
topic Research Note
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9996890/
https://www.ncbi.nlm.nih.gov/pubmed/36895043
http://dx.doi.org/10.1186/s13104-023-06289-z
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