Gene expression profiling of U12-type spliceosome mutant Drosophila reveals widespread changes in metabolic pathways.

<h4>Background</h4>The U12-type spliceosome is responsible for the removal of a subset of introns from eukaryotic mRNAs. U12-type introns are spliced less efficiently than normal U2-type introns, which suggests a rate-limiting role in gene expression. The Drosophila genome contains about...

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Autores principales:	Heli K J Pessa, Dario Greco, Jouni Kvist, Gudrun Wahlström, Tapio I Heino, Petri Auvinen, Mikko J Frilander
Formato:	article
Lenguaje:	EN
Publicado:	Public Library of Science (PLoS) 2010
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/260a911fd23640368f83c04f90b671be
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spelling	oai:doaj.org-article:260a911fd23640368f83c04f90b671be2021-11-18T07:03:29ZGene expression profiling of U12-type spliceosome mutant Drosophila reveals widespread changes in metabolic pathways.1932-620310.1371/journal.pone.0013215https://doaj.org/article/260a911fd23640368f83c04f90b671be2010-10-01T00:00:00Zhttps://www.ncbi.nlm.nih.gov/pmc/articles/pmid/20949011/?tool=EBIhttps://doaj.org/toc/1932-6203<h4>Background</h4>The U12-type spliceosome is responsible for the removal of a subset of introns from eukaryotic mRNAs. U12-type introns are spliced less efficiently than normal U2-type introns, which suggests a rate-limiting role in gene expression. The Drosophila genome contains about 20 U12-type introns, many of them in essential genes, and the U12-type spliceosome has previously been shown to be essential in the fly.<h4>Methodology/principal findings</h4>We have used a Drosophila line with a P-element insertion in U6atac snRNA, an essential component of the U12-type spliceosome, to investigate the impact of U12-type introns on gene expression at the organismal level during fly development. This line exhibits progressive accumulation of unspliced U12-type introns during larval development and the death of larvae at the third instar stage. Surprisingly, microarray and RT-PCR analyses revealed that most genes containing U12-type introns showed only mild perturbations in the splicing of U12-type introns. In contrast, we detected widespread downstream effects on genes that do not contain U12-type introns, with genes related to various metabolic pathways constituting the largest group.<h4>Conclusions/significance</h4>U12-type intron-containing genes exhibited variable gene-specific responses to the splicing defect, with some genes showing up- or downregulation, while most did not change significantly. The observed residual U12-type splicing activity could be explained with the mutant U6atac allele having a low level of catalytic activity. Detailed analysis of all genes suggested that a defect in the splicing of the U12-type intron of the mitochondrial prohibitin gene may be the primary cause of the various downstream effects detected in the microarray analysis.Heli K J PessaDario GrecoJouni KvistGudrun WahlströmTapio I HeinoPetri AuvinenMikko J FrilanderPublic Library of Science (PLoS)articleMedicineRScienceQENPLoS ONE, Vol 5, Iss 10, p e13215 (2010)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Heli K J Pessa Dario Greco Jouni Kvist Gudrun Wahlström Tapio I Heino Petri Auvinen Mikko J Frilander Gene expression profiling of U12-type spliceosome mutant Drosophila reveals widespread changes in metabolic pathways.
description	<h4>Background</h4>The U12-type spliceosome is responsible for the removal of a subset of introns from eukaryotic mRNAs. U12-type introns are spliced less efficiently than normal U2-type introns, which suggests a rate-limiting role in gene expression. The Drosophila genome contains about 20 U12-type introns, many of them in essential genes, and the U12-type spliceosome has previously been shown to be essential in the fly.<h4>Methodology/principal findings</h4>We have used a Drosophila line with a P-element insertion in U6atac snRNA, an essential component of the U12-type spliceosome, to investigate the impact of U12-type introns on gene expression at the organismal level during fly development. This line exhibits progressive accumulation of unspliced U12-type introns during larval development and the death of larvae at the third instar stage. Surprisingly, microarray and RT-PCR analyses revealed that most genes containing U12-type introns showed only mild perturbations in the splicing of U12-type introns. In contrast, we detected widespread downstream effects on genes that do not contain U12-type introns, with genes related to various metabolic pathways constituting the largest group.<h4>Conclusions/significance</h4>U12-type intron-containing genes exhibited variable gene-specific responses to the splicing defect, with some genes showing up- or downregulation, while most did not change significantly. The observed residual U12-type splicing activity could be explained with the mutant U6atac allele having a low level of catalytic activity. Detailed analysis of all genes suggested that a defect in the splicing of the U12-type intron of the mitochondrial prohibitin gene may be the primary cause of the various downstream effects detected in the microarray analysis.
format	article
author	Heli K J Pessa Dario Greco Jouni Kvist Gudrun Wahlström Tapio I Heino Petri Auvinen Mikko J Frilander
author_facet	Heli K J Pessa Dario Greco Jouni Kvist Gudrun Wahlström Tapio I Heino Petri Auvinen Mikko J Frilander
author_sort	Heli K J Pessa
title	Gene expression profiling of U12-type spliceosome mutant Drosophila reveals widespread changes in metabolic pathways.
title_short	Gene expression profiling of U12-type spliceosome mutant Drosophila reveals widespread changes in metabolic pathways.
title_full	Gene expression profiling of U12-type spliceosome mutant Drosophila reveals widespread changes in metabolic pathways.
title_fullStr	Gene expression profiling of U12-type spliceosome mutant Drosophila reveals widespread changes in metabolic pathways.
title_full_unstemmed	Gene expression profiling of U12-type spliceosome mutant Drosophila reveals widespread changes in metabolic pathways.
title_sort	gene expression profiling of u12-type spliceosome mutant drosophila reveals widespread changes in metabolic pathways.
publisher	Public Library of Science (PLoS)
publishDate	2010
url	https://doaj.org/article/260a911fd23640368f83c04f90b671be
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Gene expression profiling of U12-type spliceosome mutant Drosophila reveals widespread changes in metabolic pathways.

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