Medical Cell Biology Research Group, Department of Human Structure and Repair, Faculty of Medicine and Health Sciences, Ghent University, Ghent, Belgium.
Department of Biomolecular Medicine, Faculty of Medicine and Health Sciences, Ghent University, Ghent, Belgium.
Cytoskeleton (Hoboken). 2020 Dec;77(12):527-543. doi: 10.1002/cm.21647. Epub 2020 Dec 8.
The actin family is crucial for many cellular processes and in mammals muscle and non-muscle forms exist. The latter group contains cytoplasmic-β-actin and cytoplasmic-γ-actin, almost identical in amino acid sequence and with a significant functional overlap. We introduce the properties of the Actb gene and mRNA transcript(s) with main focus on the 3'UTR and its unique features, that is, the zipcode and two polyadenylation sites creating transcripts of different lengths. Several transgenic mouse models with a modified Actb locus have been created. The different mouse models can be divided into three groups; that is, 5' or 3' insertion models, mouse models with loxP sequences around exon 2-3 resulting in deletion the start codon, and models with gene edited Actb sequences that produces γ-actin protein instead of β-actin. Whole body knockouts and, with one exception, insertion models lead to embryonic lethality indicating that the Actb gene or transcripts or translated β-actin are essential. Tissue specific ablation at later developmental stages lead to no, or mild phenotypes, suggesting that the Actb gene or β-actin protein is somewhat dispensable. Gene edited Actb mice that produce γ-actin are viable. This assumes that the nucleotide sequence of Actb is important and not the specific amino acid sequence of the protein it encodes. Upregulation of other actin paralogs was frequently observed upon β-actin ablation and can also engage in the phenotype. For a better understanding, it will be necessary to analyze in current and future models all relevant actin transcripts and protein levels in a standardized and comprehensive way.
肌动蛋白家族对于许多细胞过程至关重要，在哺乳动物中存在肌肉和非肌肉形式。后者包含细胞质-β-肌动蛋白和细胞质-γ-肌动蛋白，在氨基酸序列上几乎相同，具有显著的功能重叠。我们介绍了 Actb 基因及其 mRNA 转录物的特性，主要关注 3'UTR 及其独特特征，即 zipcode 和两个多聚腺苷酸化位点，产生不同长度的转录物。已经创建了具有修饰的 Actb 基因座的几种转基因小鼠模型。不同的小鼠模型可以分为三组；即 5'或 3'插入模型、在exon 2-3 周围具有 loxP 序列的小鼠模型导致起始密码子缺失、以及具有基因编辑的 Actb 序列的模型，该序列产生 γ-肌动蛋白蛋白而不是 β-肌动蛋白。全身体内敲除和除一个例外外，插入模型导致胚胎致死，表明 Actb 基因或转录物或翻译的 β-肌动蛋白是必需的。在后期发育阶段的组织特异性消融导致无或轻度表型，表明 Actb 基因或 β-肌动蛋白蛋白在某种程度上是可有可无的。产生 γ-肌动蛋白的基因编辑 Actb 小鼠是可行的。这意味着 Actb 的核苷酸序列很重要，而不是它编码的蛋白质的特定氨基酸序列。在 β-肌动蛋白消融后，经常观察到其他肌动蛋白同源物的上调，并且也可以参与表型。为了更好地理解，有必要以标准化和全面的方式分析当前和未来模型中所有相关的肌动蛋白转录物和蛋白质水平。
