Alternative mRNA Splicing from the Glial Fibrillary Acidic Protein (GFAP) Gene Generates Isoforms with Distinct Subcellular mRNA Localization Patterns in Astrocytes

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The intermediate filament network of astrocytes includes Glial fibrillary acidic protein (Gfap) as a major component. Gfap mRNA is alternatively spliced resulting in generation of different protein isoforms where Gfapa is the most predominant isoform. The Gfapd isoform is expressed in proliferating neurogenic astrocytes of the developing human brain and in the adult human and mouse brain. Here we provide a characterization of mouse Gfapd mRNA and Gfapd protein. RT-qPCR analysis showed that Gfapd mRNA and Gfapa mRNA expression is coordinately increased in the post-natal period.
Immunohistochemical staining of developing mouse brain samples showed that Gfapd is expressed in the sub-ventricular zones in accordance with the described localization in the developing and adult human brain. Immunofluorescence analysis verified incorporation of Gfapd into the Gfap intermediate filament network and overlap in Gfapd and Gfapa subcellular
localization. Subcellular mRNA localization studies identified different localization patterns of Gfapd and Gfapa mRNA in mouse primary astrocytes. A larger fraction of Gfapa mRNA showed mRNA localization to astrocyte protrusions compared to Gfapd mRNA. The differential mRNA localization patterns were dependent on the different 39-exon sequences included in Gfapd and Gfapa mRNA. The presented results show that alternative Gfap mRNA splicing results in isoform-specific mRNA localization patterns with resulting different local mRNA concentration ratios which have potential to participate in
subcellular region-specific intermediate filament dynamics during brain development, maintenance and in disease
Original languageEnglish
Article numbere72110
Issue number8
Pages (from-to)1-12
Number of pages12
Publication statusPublished - Aug 2013

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