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Postnatal Dynamics of Zeb2 Expression in Rat Brain: Analysis of Novel 3' UTR Sequence Reveals a miR-9 Interacting Site


Kropivšek, Klara; Pickford, Jasmine; Carter, David A (2014). Postnatal Dynamics of Zeb2 Expression in Rat Brain: Analysis of Novel 3' UTR Sequence Reveals a miR-9 Interacting Site. Journal of Molecular Neuroscience, 52(1):138-147.

Abstract

ZEB2 is a transcription factor with established roles in neurogenesis but no defined function in postnatal brain despite extensive neuronal expression in telencephalic structures. Multiple, incompletely annotated transcripts derive from the Zeb2 locus; the purpose of the present study was to structurally characterize rat brain Zeb2 transcripts with respect to 3' untranslated (UTR) sequence in order to understand Zeb2 transcript regulation including possible interactions with regulatory molecules such as neuronal miRNAs. We cloned a 5054-nucleotide Zeb2 3' UTR that is included in the most abundant Zeb2 transcript in neonatal rat brain. Unique features of the distal 3' UTR region included a number of brain-specific miRNA target sites; a highly conserved miR-9 target site at 3' UTR position 4097 was selected for functional verification in transfection experiments. Parallel analysis of Zeb2 transcript, ZEB2 protein and miR-9 levels across postnatal brain cortical development revealed a significant accumulation of ZEB2 protein levels only between postnatal days P2 and P5 that was associated with an acute loss of postnatal miR-9 expression in cortex. These studies demonstrate novel features of Zeb2 gene expression in postnatal rat brain and highlight the importance of full transcript annotation for identifying the complement of potential transcript-interacting regulators.

Abstract

ZEB2 is a transcription factor with established roles in neurogenesis but no defined function in postnatal brain despite extensive neuronal expression in telencephalic structures. Multiple, incompletely annotated transcripts derive from the Zeb2 locus; the purpose of the present study was to structurally characterize rat brain Zeb2 transcripts with respect to 3' untranslated (UTR) sequence in order to understand Zeb2 transcript regulation including possible interactions with regulatory molecules such as neuronal miRNAs. We cloned a 5054-nucleotide Zeb2 3' UTR that is included in the most abundant Zeb2 transcript in neonatal rat brain. Unique features of the distal 3' UTR region included a number of brain-specific miRNA target sites; a highly conserved miR-9 target site at 3' UTR position 4097 was selected for functional verification in transfection experiments. Parallel analysis of Zeb2 transcript, ZEB2 protein and miR-9 levels across postnatal brain cortical development revealed a significant accumulation of ZEB2 protein levels only between postnatal days P2 and P5 that was associated with an acute loss of postnatal miR-9 expression in cortex. These studies demonstrate novel features of Zeb2 gene expression in postnatal rat brain and highlight the importance of full transcript annotation for identifying the complement of potential transcript-interacting regulators.

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Additional indexing

Item Type:Journal Article, refereed, original work
Communities & Collections:07 Faculty of Science > Department of Plant and Microbial Biology
07 Faculty of Science > Zurich-Basel Plant Science Center
Dewey Decimal Classification:580 Plants (Botany)
Language:English
Date:2014
Deposited On:11 Mar 2014 16:34
Last Modified:14 Feb 2018 21:02
Publisher:Humana Press (Springer)
ISSN:0895-8696
OA Status:Closed
Publisher DOI:https://doi.org/10.1007/s12031-013-0146-x
PubMed ID:24458742

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