RAG-1 and RAG-2, Adjacent Genes That Synergistically Activate V(D)J Recombination

TLDR

V(D)J recombination generates the diverse repertoire of immunoglobulins and T cell receptors in developing lymphocytes, and this process relies on the adjacent, evolutionarily conserved genes RAG‑1 and RAG‑2, which are expressed exclusively in maturing lymphoid cells. Coexpression of RAG‑1 with its adjacent partner RAG‑2 boosts V(D)J recombination activity by at least 1,000‑fold, indicating that the two proteins directly participate in the recombination reaction.

Abstract

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 fibroblasts, but cotransfection with an adjacent gene, RAG-2, has resulted in at least a 1000-fold increase in the frequency of recombination. 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 kilobases 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.