International Journal of Molecular Sciences,
Journal Year:
2013,
Volume and Issue:
14(8), P. 16087 - 16110
Published: Aug. 5, 2013
MicroRNAs
(miRNAs)
are
small
non-coding
RNA
molecules
acting
as
post-transcriptional
regulators
of
gene
expression.
They
involved
in
many
biological
processes,
and
their
dysregulation
is
implicated
various
diseases,
including
multiple
sclerosis
(MS).
Interferon-beta
(IFN-beta)
widely
used
a
first-line
immunomodulatory
treatment
MS
patients.
Here,
we
present
the
first
longitudinal
study
on
miRNA
expression
changes
response
to
IFN-beta
therapy.
Peripheral
blood
mononuclear
cells
(PBMC)
were
obtained
before
initiation
well
after
two
days,
four
one
month,
from
patients
with
clinically
isolated
syndrome
(CIS)
relapsing-remitting
(RRMS).
We
measured
651
mature
miRNAs
about
19,000
mRNAs
parallel
using
real-time
PCR
arrays
Affymetrix
microarrays.
observed
that
up-regulation
IFN-beta-responsive
genes
accompanied
by
down-regulation
several
miRNAs,
members
mir-29
family.
These
differentially
expressed
found
be
associated
apoptotic
processes
IFN
feedback
loops.
A
network
miRNA-mRNA
target
interactions
was
constructed
integrating
information
different
databases.
Our
results
suggest
miRNA-mediated
regulation
plays
an
important
role
mechanisms
action
IFN-beta,
not
only
but
also
normal
immune
responses.
levels
may
serve
biomarker
effects
therapy
predict
individual
disease
activity
progression.
PLoS Biology,
Journal Year:
2014,
Volume and Issue:
12(6), P. e1001874 - e1001874
Published: June 3, 2014
Mechanisms
behind
how
the
immune
system
signals
to
brain
in
response
systemic
inflammation
are
not
fully
understood.
Transgenic
mice
expressing
Cre
recombinase
specifically
hematopoietic
lineage
a
reporter
background
display
recombination
and
marker
gene
expression
Purkinje
neurons.
Here
we
show
that
reportergene
neurons
is
caused
by
intercellular
transfer
of
functional
messenger
RNA
from
cells
into
absence
cell
fusion.
In
vitro
purified
secreted
extracellular
vesicles
(EVs)
blood
contain
mRNA,
which
induces
when
injected
brain.
Although
Cre-mediated
events
occur
very
rarely
healthy
animals,
their
number
increases
considerably
different
injury
models,
particularly
under
inflammatory
conditions,
extend
beyond
other
neuronal
populations
cortex,
hippocampus,
substantia
nigra.
Recombined
differ
miRNA
profile
nonrecombined
counterparts,
indicating
physiological
significance.
These
observations
reveal
existence
previously
unrecognized
mechanism
communicate
RNA-based
between
various
organs,
including
brain,
inflammation.
Nature Communications,
Journal Year:
2015,
Volume and Issue:
6(1)
Published: Nov. 25, 2015
Abstract
microRNAs
(miRNAs)
act
as
sequence-specific
guides
for
Argonaute
(AGO)
proteins,
which
mediate
posttranscriptional
silencing
of
target
messenger
RNAs.
Despite
their
importance
in
many
biological
processes,
rules
governing
AGO–miRNA
targeting
are
only
partially
understood.
Here
we
report
a
modified
AGO
HITS-CLIP
strategy
termed
CLEAR
(covalent
ligation
endogenous
Argonaute-bound
RNAs)-CLIP,
enriches
miRNAs
ligated
to
mRNA
targets.
CLEAR-CLIP
mapped
∼130,000
miRNA–target
interactions
mouse
brain
and
∼40,000
human
hepatoma
cells.
Motif
structural
analysis
define
expanded
pairing
over
200
mammalian
miRNAs.
Most
combine
seed-based
with
distinct,
miRNA-specific
patterns
auxiliary
pairing.
At
some
regulatory
sites,
this
specificity
confers
distinct
functions
miRNA
family
members
shared
seed
sequences
but
divergent
3′-ends.
This
work
provides
means
explicit
biochemical
identification
sites
vivo
,
leading
the
discovery
that
3′-end
is
general
determinant
binding
specificity.
Neuron,
Journal Year:
2014,
Volume and Issue:
81(2), P. 294 - 305
Published: Jan. 1, 2014
Highlights•Ago2
HITS-CLIP
reveals
miRNAs
and
their
transcriptomic
binding
sites
in
human
brain•>1,800
Ago2
correspond
to
the
top
20
most
abundant
brain
miRNAs•Conserved
mouse
Ago
associate
with
synaptic
functions•Ago2
overlap
disease-relevant
polymorphisms
that
alter
miRNA
seed
pairingSummaryThe
orchestration
of
function
requires
complex
gene
regulatory
networks
are
modulated,
part,
by
microRNAs
(miRNAs).
These
noncoding
RNAs
argonaute
(Ago)
proteins
order
direct
posttranscriptional
suppression
via
base
pairing
target
transcripts.
In
better
understand
how
contribute
human-specialized
processes
neurological
phenotypes,
identifying
targets
is
paramount
importance.
Here,
we
address
latter
profiling
Ago2:RNA
interactions
using
generate
a
transcriptome-wide
map
brain.
We
uncovered
∼7,000
stringent
highly
enriched
for
conserved
sequences
corresponding
miRNAs.
This
interactome
points
functional
miRNA:target
pairs
across
>3,000
genes
represents
valuable
resource
accelerating
our
understanding
functions
demonstrate
utility
this
exploring
clinically
relevant
may
facilitate
translation
genetic
studies
neuropsychiatric
diseases
into
therapeutics.
Journal of Clinical Investigation,
Journal Year:
2015,
Volume and Issue:
125(2), P. 681 - 686
Published: Jan. 8, 2015
Tau
is
a
highly
abundant
and
multifunctional
brain
protein
that
accumulates
in
neurofibrillary
tangles
(NFTs),
most
commonly
Alzheimer's
disease
(AD)
primary
age-related
tauopathy.
Recently,
microRNAs
(miRNAs)
have
been
linked
to
neurodegeneration;
however,
it
not
clear
whether
miRNA
dysregulation
contributes
tau
neurotoxicity.
Here,
we
determined
the
conserved
miR-219
downregulated
tissue
taken
at
autopsy
from
patients
with
AD
those
severe
In
Drosophila
model
produces
human
tau,
reduction
of
exacerbated
toxicity,
while
overexpression
partially
abrogated
toxic
effects.
Moreover,
observed
bidirectional
modulation
levels
was
dependent
on
expression
or
neutralization,
demonstrating
regulates
vivo.
mammalian
cellular
models,
found
binds
directly
3'-UTR
mRNA
represses
synthesis
post-transcriptional
level.
Together,
our
data
indicate
silencing
by
an
ancient
regulatory
mechanism
may
become
perturbed
during
degeneration
suggest
this
pathway
be
useful
for
developing
therapeutics
tauopathies.
