Tissue-specific RNA splicing generates an ankyrin-like domain that affects the dimerization and DNA-binding properties of a bHLH protein.
Tissue-specific RNA splicing generates an ankyrin-like domain that affects the dimerization and DNA-binding properties of a bHLH protein.
复制标题
组织特异性 RNA 剪接产生锚蛋白样结构域，影响 bHLH 蛋白的二聚化和 DNA 结合特性。
DOI：
10.1101/gad.7.1.55
复制
发表时间：
1993
影响因子：
10.5
通讯作者：
Rosenfeld,MG
中科院分区：
文献类型：
--
作者：
Klein,ES;Simmons,DM;Swanson,LW;Rosenfeld,MG
编码两种大鼠bHLH蛋白的mRNAs，称为Rebα和Rebβ，已被鉴定为来自单个基因组座位的选择性剪接转录本。不同的RNA加工事件会导致这两个mRNAs的比率因组织而异。虽然REB基因在发育中的神经管中表现出高度丰富的表达水平，但在成熟动物的许多器官中都有不同水平的表达。Rebα序列包含一个以亮氨酸七肽重复为特征的区域，该重复位于位于羧基末端的bHLH域的氨基末端。REBβ与REBα相同，不同之处在于在亮氨酸七肽重复序列中插入了24个氨基酸，这是由于在REBβ转录本中增加了一个72个碱基的外显子。由于这一插入，Rebβ与同源E-box结合位点结合的能力明显减弱，并与bHLH基因家族的其他成员形成同源二聚体和异源二聚体。对24个氨基酸的Rebβ特异插入片段的分析表明，它介导了一种抑制功能，并显示出与Ankyrin类重复序列显著的序列相似性。有人认为，这种组织特异性的REB RNA剪接模式参与了无处不在的和组织受限的bHLH蛋白的异二聚体复合体的相应组织特异性组合的确定。因此，Rebα和Rebβ代表了一个新的例子，即在bHLH蛋白中调节形成一个锚定蛋白样结构域，从而介导蛋白质-蛋白质相互作用的控制。
mRNAs encoding two rat bHLH proteins, referred to as REB alpha and REB beta, have been identified as alternatively spliced transcripts derived from a single genomic locus. Alternative RNA processing events results in tissue-specific differences in the ratios of these two mRNAs. Although it exhibits a highly enriched level of expression in the developing neural tube, the REB gene is expressed at variable levels in many organs of the mature animal. The REB alpha sequence contains a region characterized by a leucine heptad repeat that is situated amino-terminal of the carboxy-terminally located bHLH domain. REB beta is identical to REB alpha except for a 24-amino-acid insertion in the leucine heptad repeat that results from the inclusion of an additional 72-bp exon in the REB beta transcript. As a consequence of this insertion, REB beta exhibits a markedly diminished capacity to bind to cognate E-box-binding sites and to form homodimers and heterodimers with other members of the bHLH gene family. Analysis of the 24-amino-acid REB beta-specific insert revealed that it mediates an inhibitory function and exhibits a significant degree of sequence similarity to ankyrin-like repeats. It is proposed that this tissue-specific pattern of REB RNA splicing is involved in the determination of corresponding tissue-specific combinations of heterodimeric complexes of ubiquitous and tissue-restricted bHLH proteins. Thus, REB alpha and REB beta represent a novel example of a regulated formation of an ankyrin-like domain within a bHLH protein, thereby mediating control of protein-protein interactions.