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

Overview

Journal Cell

Publisher Cell Press

Specialty Cell Biology

Date 2016 Jun 14

PMID 27293192

Citations 96

Authors

Shengfeng Huang

Xin Tao

Shaochun Yuan

Yuhang Zhang

Peiyi Li

Helen A Beilinson

Ya Zhang

Wenjuan Yu

Pierre Pontarotti

Hector Escriva

Yann le Petillon

Xiaolong Liu

Shangwu Chen

David G Schatz

Anlong Xu

Affiliations

Soon will be listed here.

Abstract

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 germline 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.

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