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Expression of SOLOIST/MRTFB i4, a novel neuronal isoform of the mouse serum response factor coactivator myocardin‐related transcription factor‐B, negatively regulates dendritic complexity in cortical neurons

Abstract Megakaryoblastic leukemia 2 (MKL2)/myocardin‐related transcription factor‐B (MRTFB), a serum response factor (SRF) coactivator, is an important regulator of gene expression and neuronal morphology. Here, we show that different mouse MRTFB splice isoforms, including a novel fourth MRTFB isoform named spliced neuronal long isoform of SRF transcriptional coactivator (SOLOIST)/MRTFB isoform 4 (MRTFB i4), play distinct roles in this process. SOLOIST/MRTFB i4 has a short exon that encodes 21 amino acid residues ahead of the first RPXXXEL (RPEL) motif in MRTFB isoform 3. Quantitative PCR revealed that SOLOIST/MRTFB i4 and isoform 1 were enriched in the forebrain and neurons, and upregulated during brain development. Conversely, isoform 3 was detected in various tissues, including both neurons and astrocytes, and was downregulated in the developing brain. Reporter assays supported the SRF‐coactivator function of SOLOIST/MRTFB i4 as well as isoform 1. Acute expression of MRTFB isoform 1, but not isoform 3 or SOLOIST/MRTFB i4, in neuronal cells within 24 h drastically increased endogenous immediate early gene (c‐fos, egr 1, and Arc ) expression, but not endogenous actinin α1 , β‐actin , gelsolin , or srf gene expression measured by qPCR. Overexpression of SOLOIST/MRTFB i4 reduced the dendritic complexity of cortical neurons, whereas overexpression of isoform 1 increased this complexity. Coexpression of isoform 1 and SOLOIST/MRTFB i4 in cortical neurons revealed that isoform 1 competitively counteracted downregulation by SOLOIST/MRTFB i4. Our findings indicate that MRTFB isoforms have unique expression patterns and differential effects on gene expression and dendritic complexity, which contribute to shaping neuronal circuits, at least in part.

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