Fig. 1: Neuronal-specificity and evolutionary conservation of Daam1-MIC. | Nature Communications

Fig. 1: Neuronal-specificity and evolutionary conservation of Daam1-MIC.

From: A highly conserved neuronal microexon in DAAM1 controls actin dynamics, RHOA/ROCK signaling, and memory formation

Fig. 1

a Heatmap showing gene expression levels of formin genes across multiple tissues and cell types based on VastDB. TPM: Transcript Per Million. b Schematic representation of the protein impact of neural-specific exons. Yellow-colored boxes represent upstream and downstream exons where the red box represents the alternatively spliced exon. GBD, GTPase-binding domain; FH3, Formin-Homology-3 domain or Diaphanous-Inhibitory Domain; FH2, Formin-Homology-2 domain. c Distribution of inclusion levels, using the Percent Spliced In (PSI) metric, for neural-specific exons in formin genes. PSI values were obtained from VastDB. Number of data points per plot and source data are provided as a Source Data file 1. d Evolutionary conservation of neural-specific alternative exons in formin genes. Black dots indicate the presence of an exon ortholog at the genome level. e Schematic representation of DAAM1 and its domains (top), together with DAAM1 protein structure based on AlphaFold2 (bottom). The location of Daam1-MIC (HsaEX0018410 in VastDB) is shown. f Partial amino acid sequence alignment of the FH2 domain of DAAM1 orthologs across vertebrates. Microexon (μ), upstream (C1), and downstream exons (C2) are indicated. The barplot depicts amino acid conservation. g Conserved neural-specificity of Daam1-MIC orthologs in vertebrates. PSI values from VastDB. h RT-PCR assays showing the inclusion of Daam1-MIC orthologs in different tissues from mice and zebrafish. i Srrm3/4-dependent regulation of Daam1-MIC orthologs in human, mouse and zebrafish. PSI values in the condition with (+, blue) or without (-, red) Srrm3/4 are shown. RNA-seq data from human HEK293 cells overexpressing human SRRM460, mouse N2A cells upon Srrm3/4 knockdown24, and zebrafish retinae extracted from Srrm3 KO 5 days post fertilization larvae61. j RT-PCR assays showing the inclusion of Daam1-MIC in cerebellum of WT and Srrm3 KO mice. h, j Inclusion and the skipping bands are indicated on the left side of the gel. PSI values are indicated below. RT-PCR assays were performed once. GBD GTPase-binding domain, FH3 Formin-Homology-3 domain or Diaphanous-Inhibitory Domain, DD Dimerization Domain, CC Coiled-Coil Domain, FH1 Formin-Homology-1 domain, FH2 Formin-Homology-2 domain, DAD Diaphanous-Autoregulatory Domain.

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