Transcriptome profiling of mouse brains with qkI-deficient oligodendrocytes reveals major alternative splicing defects including self-splicing

Abstract The qkI gene encodes a family of RNA binding proteins alternatively spliced at its 3′ end, giving rise to three major spliced isoforms: QKI-5, QKI-6 and QKI-7. Their expression is tightly regulated during brain development with nuclear QKI-5 being the most abundant during embryogenesis foll...

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Autores principales:	Lama Darbelli, Karine Choquet, Stéphane Richard, Claudia L. Kleinman
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2017
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/2b87d7231695460a91e0f2f7857ac0f8
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spelling	oai:doaj.org-article:2b87d7231695460a91e0f2f7857ac0f82021-12-02T11:41:11ZTranscriptome profiling of mouse brains with qkI-deficient oligodendrocytes reveals major alternative splicing defects including self-splicing10.1038/s41598-017-06211-12045-2322https://doaj.org/article/2b87d7231695460a91e0f2f7857ac0f82017-08-01T00:00:00Zhttps://doi.org/10.1038/s41598-017-06211-1https://doaj.org/toc/2045-2322Abstract The qkI gene encodes a family of RNA binding proteins alternatively spliced at its 3′ end, giving rise to three major spliced isoforms: QKI-5, QKI-6 and QKI-7. Their expression is tightly regulated during brain development with nuclear QKI-5 being the most abundant during embryogenesis followed by QKI-6 and QKI-7 that peak during myelination. Previously, we generated a mouse conditional qkI allele where exon 2 is excised using Olig2-Cre resulting in QKI-deficient oligodendrocytes (OLs). These mice have dysmyelination and die at the third post-natal week. Herein, we performed a transcriptomic analysis of P14 mouse brains of QKI-proficient (QKI FL/FL;- ) and QKI-deficient (QKI FL/FL;Olig2-Cre ) OLs. QKI deficiency results in major global changes of gene expression and RNA processing with >1,800 differentially expressed genes with the top categories being axon ensheathment and myelination. Specific downregulated genes included major myelin proteins, suggesting that the QKI proteins are key regulators of RNA metabolism in OLs. We also identify 810 alternatively spliced genes including known QKI targets, MBP and Nfasc. Interestingly, we observe in QKI FL/FL;Olig2-Cre a switch in exon 2-deficient qkI mRNAs favoring the expression of the qkI-5 rather than the qkI-6 and qkI-7. These findings define QKI as regulators of alternative splicing in OLs including self-splicing.Lama DarbelliKarine ChoquetStéphane RichardClaudia L. KleinmanNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 7, Iss 1, Pp 1-13 (2017)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Lama Darbelli Karine Choquet Stéphane Richard Claudia L. Kleinman Transcriptome profiling of mouse brains with qkI-deficient oligodendrocytes reveals major alternative splicing defects including self-splicing
description	Abstract The qkI gene encodes a family of RNA binding proteins alternatively spliced at its 3′ end, giving rise to three major spliced isoforms: QKI-5, QKI-6 and QKI-7. Their expression is tightly regulated during brain development with nuclear QKI-5 being the most abundant during embryogenesis followed by QKI-6 and QKI-7 that peak during myelination. Previously, we generated a mouse conditional qkI allele where exon 2 is excised using Olig2-Cre resulting in QKI-deficient oligodendrocytes (OLs). These mice have dysmyelination and die at the third post-natal week. Herein, we performed a transcriptomic analysis of P14 mouse brains of QKI-proficient (QKI FL/FL;- ) and QKI-deficient (QKI FL/FL;Olig2-Cre ) OLs. QKI deficiency results in major global changes of gene expression and RNA processing with >1,800 differentially expressed genes with the top categories being axon ensheathment and myelination. Specific downregulated genes included major myelin proteins, suggesting that the QKI proteins are key regulators of RNA metabolism in OLs. We also identify 810 alternatively spliced genes including known QKI targets, MBP and Nfasc. Interestingly, we observe in QKI FL/FL;Olig2-Cre a switch in exon 2-deficient qkI mRNAs favoring the expression of the qkI-5 rather than the qkI-6 and qkI-7. These findings define QKI as regulators of alternative splicing in OLs including self-splicing.
format	article
author	Lama Darbelli Karine Choquet Stéphane Richard Claudia L. Kleinman
author_facet	Lama Darbelli Karine Choquet Stéphane Richard Claudia L. Kleinman
author_sort	Lama Darbelli
title	Transcriptome profiling of mouse brains with qkI-deficient oligodendrocytes reveals major alternative splicing defects including self-splicing
title_short	Transcriptome profiling of mouse brains with qkI-deficient oligodendrocytes reveals major alternative splicing defects including self-splicing
title_full	Transcriptome profiling of mouse brains with qkI-deficient oligodendrocytes reveals major alternative splicing defects including self-splicing
title_fullStr	Transcriptome profiling of mouse brains with qkI-deficient oligodendrocytes reveals major alternative splicing defects including self-splicing
title_full_unstemmed	Transcriptome profiling of mouse brains with qkI-deficient oligodendrocytes reveals major alternative splicing defects including self-splicing
title_sort	transcriptome profiling of mouse brains with qki-deficient oligodendrocytes reveals major alternative splicing defects including self-splicing
publisher	Nature Portfolio
publishDate	2017
url	https://doaj.org/article/2b87d7231695460a91e0f2f7857ac0f8
work_keys_str_mv	AT lamadarbelli transcriptomeprofilingofmousebrainswithqkideficientoligodendrocytesrevealsmajoralternativesplicingdefectsincludingselfsplicing AT karinechoquet transcriptomeprofilingofmousebrainswithqkideficientoligodendrocytesrevealsmajoralternativesplicingdefectsincludingselfsplicing AT stephanerichard transcriptomeprofilingofmousebrainswithqkideficientoligodendrocytesrevealsmajoralternativesplicingdefectsincludingselfsplicing AT claudialkleinman transcriptomeprofilingofmousebrainswithqkideficientoligodendrocytesrevealsmajoralternativesplicingdefectsincludingselfsplicing
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Transcriptome profiling of mouse brains with qkI-deficient oligodendrocytes reveals major alternative splicing defects including self-splicing

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