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J Neurochem. 2015 Aug;134(3):578-89. doi: 10.1111/jnc.13136. Epub 2015 May 14.

Novel splice variants in the 5'UTR of Gtf2i expressed in the rat brain: alternative 5'UTRs and differential expression in the neuronal dendrites.

Author information

1
Department of Neuroplasticity, Institute of Pathogenesis and Disease Prevention, Shinshu University Graduate School of Medicine, Matsumoto, Japan.
2
Department of Anatomy, Hokkaido University Graduate School of Medicine, Sapporo, Japan.
3
Department of Anatomy, Kitasato University School of Medicine, Sagamihara, Japan.
4
Department of Biological Sciences for Intractable Neurological Diseases, Institute for Biomedical Sciences, Interdisciplinary Cluster for Cutting Edge Research, Shinshu University, Matsumoto, Japan.

Abstract

General transcription factor II-I (Gtf2i) is a transcription factor and one of the genes implicated in Willams-Beuren syndrome, an autism spectrum disorder. In this study, we investigated splice variants of the Gtf2i gene in both the 5'untranslated region (5'UTR) and the coding region. To search for novel 5'UTRs of Gtf2i, we utilized the cap analysis gene expression database of the mouse. We identified seven novel Gtf2i transcripts with alternatively spliced 5'UTRs in the rat brain. We also identified four novel splice variants in the coding sequence of Gtf2i. Furthermore, we identified a selective usage of certain types of 5'UTR by coding variants. In situ hybridization demonstrated a differential pattern of expression of Gtf2i mRNAs with alternatively spliced 5'UTRs among neuronal cells, and the localization of one of the variants in neuronal dendrites in the rat brain. Immunohistochemistry also demonstrated a distribution of Gtf2i-immunoreactivity in the dendrites. These results suggest multiple pathways of expression of Gtf2i gene in the brain. The expression patterns may be under the control of alternative promoters coupled to the alternative splicing in the coding region. Differential localization of mRNA to neuronal dendrites suggests spatiotemporal-specific translation at the post-synaptic sites that is involved in transfer of synaptic activity to expression of specific sets of genes in the nucleus. Gtf2i is a transcription factor and implicated in Willams-Beuren syndrome. We identified seven novel Gtf2i transcripts with alternatively spliced 5'UTRs in the rat brain. In situ hybridization demonstrated a differential expression of Gtf2i mRNAs with different 5'UTRs in somas and dendrites of neuronal cells. Differential localization of mRNA to neuronal dendrites suggests spatiotemporal-specific translation at the postsynaptic sites. The scheme shows genomic structure showing the positions of the potential transcription start tags (rDEC695, rDEC3D7, rDEC1D3, rDEC104, rDEC072 and rDEBE25). Newly identified exons (1.1-1.6) are shown with the white boxes. The distances from rDEC695-5'end are indicated in bp.

KEYWORDS:

5'UTR; Gtf2i; alternative splicing; dendrite, synaptic plasticity; mRNA

PMID:
25913238
DOI:
10.1111/jnc.13136
[Indexed for MEDLINE]
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