Anthology of Human Repetitive DNA
263
3.1
Non-LTR Retrotransposons
Detectable copies of non-LTR retrotrans-
posons contribute
34% of the human
genome compared to the
11% repre-
senting other detectable interspersed re-
peats. Non-LTR retroelements appear to be
strictly intracellular parasites, inherited for
millions of years rather than passed hori-
zontally. For historical reasons, some au-
tonomous non-LTR retrotransposons are
referred to as long interspersed repeats
(LINEs) due to the fact that they are several
kilobases long. Analogously, their short
nonautonomous associates are referred to
as short interspersed repeats (SINEs). Au-
tonomous non-LTR retrotransposons in
eukaryotic species are currently divided
into 13 superfamilies or clades: L1, CRE,
NeSL,R4,R2,RTE,Tad1,R1,LOA,I,Ingi,
Jockey, CR1, and Penelope. Only two of
them, L1 and CR1 superfamilies are repre-
sented in the human genome. The human
population continues to carry active el-
ements of L1 non-LTR retrotransposons
whereas CR1-like retroelements are ex-
tinct. L1-dependent Alu and SINE, VNTRs
and ALU (SVA) nonautonomous retroele-
ments also continue to proliferate in the
human population.
3.1.1
L1 Non-LTR Retrotransposons
The typical L1 (or LINE1) autonomous
retrotransposon is
6 kb long, and con-
tains two open reading frames referred to
as ORF1 and ORF2, encoding the
500-
aa and
1000-aa proteins, respectively
(Fig. 3). The function of the L1-ORF1p pro-
tein is not well understood. Since it has a
common leucine zipper (LZ) motif present
in its sequence, it presumably binds
RNA/DNA molecules. The L1-ORF2 pro-
tein includes the apurinic–apyrimidinic
endonuclease (APE), reverse transcrip-
tase (RT), and conserved cysteine-rich
(C) domains. The endonuclease domain is
involved in nicking the host DNA, followed
by priming of an RNA-directed DNA syn-
thesis that is catalyzed by the RT domain.
Out of several hundred thousand L1
copies present in the human genome,
about 5000 are full-length elements and
only around 100 contain intact open read-
ing frames. In addition to ORF1 and ORF2,
the full-length L1 elements contain 5
0
and
3
0
untranslated regions (UTRs), each sev-
eral hundred bp long. The 5
0
UTR includes
a poorly characterized internal pol II tran-
scription promoter. Unlike most human
genes that contain pol II promoters up-
stream of the transcription start site, the
L1 promoter is located downstream of the
start site. Occasionally, the 5
0
L1 UTR may
also promote transcription that starts in
the strand complementary to the 5
0
UTR
and extends to the genomic region flank-
ing the L1 5
0
end. The 3
0
L1 UTR includes
an AATAAA polyadenylation signal and a
polyA tail.
In addition to the transcription, the L1
life cycle includes export of the transcribed
ORF1
ORF2
pol II
AATAAA (A)
n
[TSD]
APE
RT
C
LZ
3
UTR
5
UTR
[TSD]
Fig. 3
Schematic structure of the L1 non-LTR retrotransposon. It consists of a 5
0
untranslated region (5
0
UTR) with pol II internal promoter, two open reading frames (ORF1
and ORF2), a 3
0
untranslated region, a polyA signal (AATAAA), and a polyA tail. L1 elements
are flanked by target site duplications (TSDs). The ORF1 protein includes a conserved leucine
zipper motif (LZ). The ORF2 protein includes domains for the apurinic/apyrimidinic-like
endonuclease (APE), RT, and a conserved cysteine-rich motif (C).
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