RAG-1 AND RAG-2, ADJACENT GENES THAT SYNERGISTICALLY ACTIVATE V(D)J RECOMBINATION
RAG-1 AND RAG-2, ADJACENT GENES THAT SYNERGISTICALLY ACTIVATE V(D)J RECOMBINATION
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DOI：
10.1126/science.2360047
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发表时间：
1990-06-22
期刊：
影响因子：
56.9
通讯作者：
BALTIMORE, D
中科院分区：
文献类型：
--
作者：
OETTINGER, MA;SCHATZ, DG;BALTIMORE, D
免疫球蛋白和T细胞受体的大量库部分地通过V（D）J重组产生，V（D）J重组是特异性地发生在发育中的淋巴细胞中的一系列基因组重排。重组激活基因RAG-1是一种只在成熟淋巴细胞中表达的基因，已被分离出来。当RAG-1转染成纤维细胞时，不能有效地诱导V（D）J重组酶活性，但与相邻基因RAG-2共转染，导致重组频率至少增加1000倍。2.1-脱氢酶RAG-2互补DNA编码527个氨基酸的推定蛋白质，其序列与RAG-1的序列无关。与RAG-1一样，RAG-2在进行V（D）J重组的物种之间是保守的，并且其表达模式与V（D）J重组酶活性的表达模式精确相关。除了仅相隔8个外显子外，这些会聚转录的基因是不寻常的，因为它们的编码序列和3“非翻译序列中的大多数（如果不是全部的话）包含在单个外显子中。RAG-1和RAG-2可能激活V（D）J重组酶的表达，但更可能的是，它们直接参与重组反应。
The vast repertoire of immunoglobulins and T cell receptors is generated, in part, by V(D)J recombination, a series of genomic rearrangements that occur specifically in developing lymphocytes. The recombination activating gene, RAG-1, which is a gene expressed exclusively in maturing lymphoid cells, was previously isolated. RAG-1 inefficiently induced V(D)J recombinase activity when transfected into fibroblast, but contransfection with an adjacent gene, RAG-2, has resulted in at least 1000-fold increase in the frequency of recombinantion. The 2.1-kilobase RAG-2 complementary DNA encodes a putative protein of 527 amino acids whose sequence is unrelated to that of RAG-1. Like RAG-1, RAG-2 is conserved between species that carry out V(D)J recombination, and its expression pattern correlates precisely with that of V(D)J recombinase activity. In addition to being located just 8 kilobase apart, these convergently transcribed genes are unusual in that most, if not all, of their coding and 3'' untranslated sequences are contained in single exons. RAG-1 and RAG-2 might activate the expression of the V(D)J recombinase but, more likely, they directly participate in the recombination reaction.