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Kaposi's sarcoma-associated herpesvirus encodes a mimic of cellular miR-23.
[primary effusion lymphoma]
Kaposi
's
sarcoma
-associated
herpesvirus
(
KSHV
)
expresses
∼
20
viral
microRNAs
(
miRNAs
)
in
latently
infected
cells
.
We
have
previously
shown
that
two
of
these
miRNAs
function
as
mimics
of
the
cellular
miRNAs
miR-
155
and
miR-
142
-
3
p
.
Two
additional
KSHV
miRNAs
,
miR-K
3
+
1
and
miR-K
3
,
share
perfect
and
offset
5
'
homology
with
cellular
miR-
23
,
respectively
.
Here
,
we
report
a
single
nucleotide
polymorphism
that
causes
miR-K
3
+
1
expression
in
a
subset
of
KSHV-infected
primary
effusion
lymphoma
cell
lines
as
a
consequence
of
altered
processing
of
the
primary
transcript
by
the
Microprocessor
complex
.
We
confirm
that
miR-K
3
+
1
regulates
miR-
23
targets
,
which
is
expected
because
these
miRNAs
share
the
entire
seed
region
(
nucleotides
2
to
8
)
.
Surprisingly
,
we
found
that
miR-K
3
also
regulates
miR-
23
targets
,
despite
offset
seed
sequences
.
In
addition
,
the
offset
homology
of
miR-K
3
to
miR-
23
likely
allows
this
viral
miRNA
to
expand
its
target
repertoire
beyond
the
targets
of
miR-
23
.
Because
miR-
23
is
highly
expressed
in
endothelial
cells
but
expressed
at
only
low
levels
in
B
cells
,
we
hypothesize
that
miR-K
3
may
function
to
introduce
miR-
23
-
like
activities
into
KSHV-infected
B
cells
.
Together
,
our
data
demonstrate
that
KSHV
has
evolved
at
least
three
distinct
viral
miRNAs
to
tap
into
evolutionarily
conserved
cellular
miRNA-regulatory
networks
.
Furthermore
,
our
data
allow
fundamental
insights
into
the
generation
and
functional
impact
of
miRNA
5
'
end
variation
.
Diseases
Validation
Diseases presenting
"single nucleotide polymorphism"
symptom
cadasil
dystrophic epidermolysis bullosa
erythropoietic protoporphyria
esophageal adenocarcinoma
esophageal carcinoma
kabuki syndrome
monosomy 21
oligodontia
primary effusion lymphoma
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