The promoter of the pri-miR-375 gene directs expression selectively to the endocrine pancreas.

microRNAs (miRNAs) are known to play an essential role in controlling a broad range of biological processes including animal development. Accordingly, many miRNAs are expressed preferentially in one or a small number of cell types. Yet the mechanisms responsible for this selectivity are not well und...

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Autores principales:	Tali Avnit-Sagi, Lia Kantorovich, Sharon Kredo-Russo, Eran Hornstein, Michael D Walker
Formato:	article
Lenguaje:	EN
Publicado:	Public Library of Science (PLoS) 2009
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/c51ef16d03554e6ca4d138cb6cf5e292
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spelling	oai:doaj.org-article:c51ef16d03554e6ca4d138cb6cf5e2922021-11-25T06:16:19ZThe promoter of the pri-miR-375 gene directs expression selectively to the endocrine pancreas.1932-620310.1371/journal.pone.0005033https://doaj.org/article/c51ef16d03554e6ca4d138cb6cf5e2922009-01-01T00:00:00Zhttps://www.ncbi.nlm.nih.gov/pmc/articles/pmid/19343226/pdf/?tool=EBIhttps://doaj.org/toc/1932-6203microRNAs (miRNAs) are known to play an essential role in controlling a broad range of biological processes including animal development. Accordingly, many miRNAs are expressed preferentially in one or a small number of cell types. Yet the mechanisms responsible for this selectivity are not well understood. The aim of this study was to elucidate the molecular basis of cell-specific expression of the pri-miR-375 gene, which is selectively expressed in pancreatic islets, and has been implicated both in the development of islets, and the function of mature pancreatic beta cells. An evolutionarily conserved 768 bp region of DNA upstream of the pri-miR-375 gene was linked to GFP and luciferase reporter genes, and expression monitored in transgenic mice and transfected cultured cells. Deletion and targeted mutagenesis analysis was used to evaluate the functional significance of sequence blocks within the upstream fragment. 5'-RACE analysis was used for mapping the pri-miR-375 gene transcription start site. The conserved 768 bp region was able to direct preferential expression of a GFP reporter gene to pancreatic islets in transgenic mice. Deletion analysis using a luciferase reporter gene in transfected cultured cell lines confirmed the cell specificity of the putative promoter region, and identified several key cis-elements essential for optimal activity, including E-boxes and a TATA sequence. Consistent with this, 5'-RACE analysis identified a transcription start site within this DNA region, 24 bp downstream of the TATA sequence. These studies define the promoter of the pri-miR-375 gene, and show that islet-specific expression of the pri-miR-375 gene is controlled at the transcriptional level. Detailed analysis of the transcriptional mechanisms controlling expression of miRNA genes will be essential to permit a comprehensive understanding of the complex role of miRNAs such as miR-375 in developmental processes.Tali Avnit-SagiLia KantorovichSharon Kredo-RussoEran HornsteinMichael D WalkerPublic Library of Science (PLoS)articleMedicineRScienceQENPLoS ONE, Vol 4, Iss 4, p e5033 (2009)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Tali Avnit-Sagi Lia Kantorovich Sharon Kredo-Russo Eran Hornstein Michael D Walker The promoter of the pri-miR-375 gene directs expression selectively to the endocrine pancreas.
description	microRNAs (miRNAs) are known to play an essential role in controlling a broad range of biological processes including animal development. Accordingly, many miRNAs are expressed preferentially in one or a small number of cell types. Yet the mechanisms responsible for this selectivity are not well understood. The aim of this study was to elucidate the molecular basis of cell-specific expression of the pri-miR-375 gene, which is selectively expressed in pancreatic islets, and has been implicated both in the development of islets, and the function of mature pancreatic beta cells. An evolutionarily conserved 768 bp region of DNA upstream of the pri-miR-375 gene was linked to GFP and luciferase reporter genes, and expression monitored in transgenic mice and transfected cultured cells. Deletion and targeted mutagenesis analysis was used to evaluate the functional significance of sequence blocks within the upstream fragment. 5'-RACE analysis was used for mapping the pri-miR-375 gene transcription start site. The conserved 768 bp region was able to direct preferential expression of a GFP reporter gene to pancreatic islets in transgenic mice. Deletion analysis using a luciferase reporter gene in transfected cultured cell lines confirmed the cell specificity of the putative promoter region, and identified several key cis-elements essential for optimal activity, including E-boxes and a TATA sequence. Consistent with this, 5'-RACE analysis identified a transcription start site within this DNA region, 24 bp downstream of the TATA sequence. These studies define the promoter of the pri-miR-375 gene, and show that islet-specific expression of the pri-miR-375 gene is controlled at the transcriptional level. Detailed analysis of the transcriptional mechanisms controlling expression of miRNA genes will be essential to permit a comprehensive understanding of the complex role of miRNAs such as miR-375 in developmental processes.
format	article
author	Tali Avnit-Sagi Lia Kantorovich Sharon Kredo-Russo Eran Hornstein Michael D Walker
author_facet	Tali Avnit-Sagi Lia Kantorovich Sharon Kredo-Russo Eran Hornstein Michael D Walker
author_sort	Tali Avnit-Sagi
title	The promoter of the pri-miR-375 gene directs expression selectively to the endocrine pancreas.
title_short	The promoter of the pri-miR-375 gene directs expression selectively to the endocrine pancreas.
title_full	The promoter of the pri-miR-375 gene directs expression selectively to the endocrine pancreas.
title_fullStr	The promoter of the pri-miR-375 gene directs expression selectively to the endocrine pancreas.
title_full_unstemmed	The promoter of the pri-miR-375 gene directs expression selectively to the endocrine pancreas.
title_sort	promoter of the pri-mir-375 gene directs expression selectively to the endocrine pancreas.
publisher	Public Library of Science (PLoS)
publishDate	2009
url	https://doaj.org/article/c51ef16d03554e6ca4d138cb6cf5e292
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The promoter of the pri-miR-375 gene directs expression selectively to the endocrine pancreas.

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