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

<div><p>The intermediate filament network of astrocytes includes Glial fibrillary acidic protein (Gfap) as a major component. <i>Gfap</i> mRNA is alternatively spliced resulting in generation of different protein isoforms where Gfapα is the most predominant isoform. The Gfapδ 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 <i>Gfapδ</i> mRNA and Gfapδ protein. RT-qPCR analysis showed that <i>Gfapδ</i> mRNA and <i>Gfapα</i> mRNA expression is coordinately increased in the post-natal period. Immunohistochemical staining of developing mouse brain samples showed that Gfapδ 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 Gfapδ into the Gfap intermediate filament network and overlap in Gfapδ and Gfapα subcellular localization. Subcellular mRNA localization studies identified different localization patterns of <i>Gfapδ</i> and <i>Gfapα</i> mRNA in mouse primary astrocytes. A larger fraction of <i>Gfapα</i> mRNA showed mRNA localization to astrocyte protrusions compared to <i>Gfapδ</i> mRNA. The differential mRNA localization patterns were dependent on the different 3′-exon sequences included in <i>Gfapδ</i> and <i>Gfapα</i> mRNA. The presented results show that alternative <i>Gfap</i> 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.</p>