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2016 ; 4
(ä): 14
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Post-Transcriptional Control of LINE-1 Retrotransposition by Cellular Host
Factors in Somatic Cells
#MMPMID27014690
Pizarro JG
; Cristofari G
Front Cell Dev Biol
2016[]; 4
(ä): 14
PMID27014690
show ga
Long INterspersed Element-1 (LINE-1 or L1) retrotransposons form the only
autonomously active family of transposable elements in humans. They are expressed
and mobile in the germline, in embryonic stem cells and in the early embryo, but
are silenced in most somatic tissues. Consistently, they play an important role
in individual genome variations through insertional mutagenesis and sequence
transduction, which occasionally lead to novel genetic diseases. In addition,
they are reactivated in nearly half of the human epithelial cancers, contributing
to tumor genome dynamics. The L1 element codes for two proteins, ORF1p and ORF2p,
which are essential for its mobility. ORF1p is an RNA-binding protein with
nucleic acid chaperone activity and ORF2p possesses endonuclease and reverse
transcriptase activities. These proteins and the L1 RNA assemble into a
ribonucleoprotein particle (L1 RNP), considered as the core of the
retrotransposition machinery. The L1 RNP mediates the synthesis of new L1 copies
upon cleavage of the target DNA and reverse transcription of the L1 RNA at the
target site. The L1 element takes benefit of cellular host factors to complete
its life cycle, however several cellular pathways also limit the cellular
accumulation of L1 RNPs and their deleterious activities. Here, we review the
known cellular host factors and pathways that regulate positively or negatively
L1 retrotransposition at post-transcriptional level, in particular by interacting
with the L1 machinery or L1 replication intermediates; and how they contribute to
control L1 activity in somatic cells.