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Article Dans Une Revue Cell Année : 2016

Discovery of an Active RAG Transposon Illuminates the Origins of V(D)J Recombination

Résumé

Co-option of RAG1 and RAG2 for antigen receptor gene assembly by V(D)J recombination was a crucial event in the evolution of jawed vertebrate adaptive immunity. RAG1/2 are proposed to have arisen from a transposable element, but definitive evidence for this is lacking. Here, we report the discovery of ProtoRAG, a DNA transposon family from lancelets, the most basal extant chordates. A typical ProtoRAG is flanked by 5-bp target site duplications and a pair of terminal inverted repeats (TIRs) resembling V(D) J recombination signal sequences. Between the TIRs reside tail-to-tail-oriented, intron-containing RAG1-like and RAG2-like genes. We demonstrate that ProtoRAG was recently active in the lancelet germ-line and that the lancelet RAG1/2-like proteins can mediate TIR-dependent transposon excision, host DNA recombination, transposition, and low-efficiency TIR rejoining using reaction mechanisms similar to those used by vertebrate RAGs. We propose that ProtoRAG represents a molecular "living fossil" of the long-sought RAG transposon.

Dates et versions

hal-01486940 , version 1 (10-03-2017)

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Shengfeng Huang, Xin Tao, Shaochun Yu, Yuhang Yu, Peiyi Li, et al.. Discovery of an Active RAG Transposon Illuminates the Origins of V(D)J Recombination. Cell, 2016, 166 (1), pp.102 - 114. ⟨10.1016/j.cell.2016.05.032⟩. ⟨hal-01486940⟩
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