Mittaz L, Scott H S, Rossier C, Seeburg P H, Higuchi M, Antonarakis S E
Department of Genetics and Microbiology, University of Geneva Medical School, Switzerland.
Genomics. 1997 Apr 15;41(2):210-7. doi: 10.1006/geno.1997.4655.
RED1 is a double-stranded RNA-specific editase characterized in the rat and is implicated in the editing of glutamate receptor subunit pre-mRNAs, particularly in the brain. Starting from human ESTs homologous to the rat RED1 sequence, we have characterized two forms of human RED1 cDNAs, one form coding for a putative peptide of 701 amino acids (similar to the shorter of two rat mRNAs) and a long form coding for a putative protein of 741 amino acids, the extra 120 bp of which are homologous to an AluJ sequence. Both forms were observed at approximately equal levels in cDNA clones and in seven different human tissues tested by RT-PCR. The human and rat short isoforms have 95 and 85% sequence identity at the amino acid and nucleotide levels, respectively. The human sequence (designated ADARB1 by the HGMW Nomenclature Committee) contains two double-stranded RNA-binding domains and a deaminase domain implicated in its editing action. Northern blot analysis detected two transcripts of 8.8 and 4.2 kb strongly expressed in brain and in many human adult and fetal tissues. ADARB1 maps to human chromosome 21q22.3, a region to which several genetic disorders map, including one form of bipolar affective disorder. Recently it was shown that heterozygous mice harboring an editing-incompetent glutamate receptor B allele have early onset fatal epilepsy. Since glutamate receptor channels are essential elements in synaptic function and plasticity and mediate pathology in many neurological disorders, and since RED1 is central in glutamate receptor channel control, ADARB1 is a candidate gene for diseases with neurological symptoms, such as bipolar affective disorder and epilepsy.
RED1是一种在大鼠中得到表征的双链RNA特异性编辑酶，与谷氨酸受体亚基前体mRNA的编辑有关，特别是在大脑中。从与大鼠RED1序列同源的人类ESTs出发，我们表征了两种形式的人类RED1 cDNA，一种形式编码一个推定的701个氨基酸的肽（类似于大鼠两种mRNA中较短的那种），另一种长形式编码一个推定的741个氨基酸的蛋白质，其额外的120 bp与一个AluJ序列同源。在cDNA克隆以及通过RT-PCR检测的七种不同人类组织中，两种形式的表达水平大致相等。人类和大鼠的短异构体在氨基酸和核苷酸水平上的序列同一性分别为95%和85%。人类序列（由HGMW命名委员会指定为ADARB1）包含两个双链RNA结合结构域和一个与其编辑作用有关的脱氨酶结构域。Northern印迹分析检测到8.8 kb和4.2 kb的两种转录本，在大脑以及许多人类成人和胎儿组织中强烈表达。ADARB1定位于人类染色体21q22.3，该区域与几种遗传疾病相关，包括一种双相情感障碍。最近有研究表明，携带编辑功能缺陷的谷氨酸受体B等位基因的杂合小鼠患有早发性致命癫痫。由于谷氨酸受体通道是突触功能和可塑性的关键要素，并在许多神经疾病中介导病理过程，且由于RED1在谷氨酸受体通道控制中起核心作用，ADARB1是诸如双相情感障碍和癫痫等具有神经症状疾病的候选基因。
