Article ; Online: Discovery of an Active RAG Transposon Illuminates the Origins of V(D)J Recombination.
2016 Volume 166, Issue 1, Page(s) 102–114
Abstract: Co-option of RAG1 and RAG2 for antigen receptor gene assembly by V(D)J recombination was a crucial ... target site duplications and a pair of terminal inverted repeats (TIRs) resembling V(D)J recombination ... that ProtoRAG represents a molecular "living fossil" of the long-sought RAG transposon. ...
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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MeSH term(s) | Animals ; DNA Transposable Elements ; DNA-Binding Proteins ; Evolution, Molecular ; Homeodomain Proteins ; Lancelets/genetics ; Terminal Repeat Sequences ; V(D)J Recombination |
Chemical Substances | DNA Transposable Elements ; DNA-Binding Proteins ; Homeodomain Proteins ; V(D)J recombination activating protein 2 ; RAG-1 protein (128559-51-3) |
Language | English |
Publishing date | 2016-06-09 |
Publishing country | United States |
Document type | Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't |
ZDB-ID | 187009-9 |
ISSN | 1097-4172 ; 0092-8674 |
ISSN (online) | 1097-4172 |
ISSN | 0092-8674 |
DOI | 10.1016/j.cell.2016.05.032 |
Database | MEDical Literature Analysis and Retrieval System OnLINE |
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