Journal of genetics and genomics/Journal of Genetics and Genomics,
Год журнала:
2023,
Номер
51(2), С. 208 - 221
Опубликована: Дек. 28, 2023
Inherited
retinal
dystrophies
(IRDs)
are
major
causes
of
visual
impairment
and
irreversible
blindness
worldwide,
while
the
precise
molecular
genetic
mechanisms
still
unexclusive.
N6-methyladenosine
(m6A)
modification
is
most
prevalent
internal
in
eukaryotic
mRNA.
YTH
domain
containing
2
(YTHDC2),
an
m6A
reader
protein,
has
recently
been
identified
as
a
key
player
germline
development
human
cancer.
However,
its
contribution
to
function
remains
unknown.
Here,
we
explore
role
YTHDC2
rod
photoreceptors
by
generating
rod-specific
Ythdc2
knockout
mice.
Results
show
that
deficiency
rods
diminished
scotopic
ERG
responses
progressive
degeneration.
Multi-omics
analysis
further
identifies
Ppef2
Pde6b
potential
targets
retina.
Specifically,
via
domain,
recognizes
binds
m6A-modified
mRNA
at
coding
sequence
5'-UTR,
resulting
enhanced
translation
efficiency
without
affecting
levels.
Compromised
after
depletion
ultimately
leads
decreased
protein
levels
retina,
impaired
function,
death.
Collectively,
our
finding
highlights
importance
photoreceptor
survival,
which
provides
unreported
elucidation
IRD
pathogenesis
epitranscriptomics.
Biomolecules,
Год журнала:
2025,
Номер
15(2), С. 157 - 157
Опубликована: Янв. 21, 2025
N6-methyladenosine
(m6A)
is
the
most
abundant,
dynamically
reversible,
and
evolutionarily
conserved
internal
chemical
modification
in
eukaryotic
RNA.
It
emerging
as
critical
for
regulating
gene
expression
at
post-transcriptional
level
by
affecting
RNA
metabolism
through,
example,
pre-mRNA
processing,
mRNA
decay,
translation.
ALKBH5
has
recently
been
identified
an
endogenous
m6A
demethylase
implicated
a
multitude
of
biological
processes.
This
review
provides
overview
structural
functional
characteristics
involvement
diverse
human
diseases,
including
metabolic,
immune,
reproductive,
nervous
system
disorders,
well
development
inhibitors.
In
summation,
this
highlights
current
understanding
structure,
functions,
detailed
mechanisms
various
physiological
pathological
processes
valuable
insights
clinical
applications
foundational
research
within
related
fields.
Cells,
Год журнала:
2025,
Номер
14(7), С. 521 - 521
Опубликована: Апрель 1, 2025
Mastitis
poses
a
severe
threat
to
the
global
cattle
industry,
causing
huge
economic
losses.
Environmental
mastitis
is
mainly
induced
by
Escherichia
coli
(E.
coli),
and
current
treatment
still
using
antibiotics,
with
problems
such
as
drug
resistance
food
safety.
ALKBH5
an
RNA
m6A
demethylase
that
plays
important
role
in
various
biological
processes,
while
p65
key
regulator
of
inflammatory
responses.
Therefore,
studying
interaction
between
protecting
mammary
epithelial
barrier
provides
new
insights
into
pathogenesis
mastitis.
This
study
revealed
E.
coli-induced
acute
inflammation
activated
NF-κB/p65
signaling
pathway
disrupted
cell
tight
junctions.
Knockdown
promoted
phosphorylation
inhibited
expressions
junction
proteins
TJP1,
CDH1,
OCLN.
Furthermore,
motif
analysis,
CHIP-PCR,
dual
luciferase
assay
confirmed
phosphorylated
TJP1
promoter
activity,
thereby
inhibiting
expression.
In
addition,
mouse
experiment
further
demonstrated
knockdown
aggravated
disruption,
invasion
proliferation.
Significantly,
this
first
demonstrate
details
declare
molecular
mechanism
improving
junction,
which
lays
potential
target
theoretical
foundation
for
other
infectious
diseases.
Investigative Ophthalmology & Visual Science,
Год журнала:
2024,
Номер
65(6), С. 17 - 17
Опубликована: Июнь 11, 2024
Purpose:
N
6-methyladenosine
(m6A)
methylation
is
a
chemical
modification
that
occurs
on
RNA
molecules,
where
the
hydrogen
atom
of
adenine
(A)
nucleotides
replaced
by
methyl
group,
forming
N6-methyladenosine.
This
dynamic
and
reversible
process
plays
crucial
role
in
regulating
various
biological
processes,
including
stability,
transport,
translation,
degradation.
Currently,
there
lack
research
m6A
modifications
maintaining
characteristics
RPE
cells.
readers
play
executing
functions
modifications,
which
prompted
our
investigation
into
their
regulatory
roles
RPE.
Methods:
Phagocytosis
assays,
immunofluorescence
staining,
flow
cytometry
experiments,
β-galactosidase
sequencing
(RNA-seq)
were
conducted
to
assess
functional
cellular
changes
retinal
pigment
epithelium
(RPE)
cells
following
short-hairpin
RNA–mediated
knockdown
insulin-like
growth
factor
2
mRNA-binding
protein
(IGF2BP2).
RNA-seq
ultraviolet
crosslinking
immunoprecipitation
with
high-throughput
(HITS-CLIP)
employed
identify
target
genes
regulated
IGF2BP2.
adeno-associated
virus
(AAV)
subretinal
injection
was
performed
6-
8-week-old
C57
mice
reduce
IGF2BP2
expression
RPE,
impact
mouse
visual
function
assessed
using
immunofluorescence,
quantitative
real-time
PCR,
optical
coherence
tomography,
electroretinography.
Results:
found
have
pronounced
effect
phagocytosis.
Subsequent
in-depth
exploration
revealed
modulates
mRNA
stability
PAX6
OTX2,
loss
induces
inflammatory
aging
phenotypes
impaired
function,
leading
dysfunction
vivo.
Conclusions:
Our
data
suggest
as
an
reader
homeostasis
making
it
potential
for
preventing
occurrence
diseases
related
malfunction.
The FASEB Journal,
Год журнала:
2024,
Номер
38(14)
Опубликована: Июль 14, 2024
Abstract
Sevoflurane,
as
a
commonly
used
inhaled
anesthetic
for
pediatric
patients,
has
been
reported
that
multiple
sevoflurane
exposures
are
associated
with
greater
risk
of
developing
neurocognitive
disorder.
N6‐Methyladenosine
(m6A),
the
most
common
mRNA
modification
in
eukaryotes,
emerged
crucial
regulator
brain
function
processes
involving
synaptic
plasticity,
learning
and
memory,
neurodevelopment.
Nevertheless,
relevance
m6A
RNA
methylation
exposure‐induced
developmental
neurotoxicity
remains
mostly
elusive.
Herein,
we
evaluated
genome‐wide
gene
expression
hippocampus
mice
received
using
m6A‐sequencing
(m6A‐seq)
RNA‐sequencing
(RNA‐seq).
We
discovered
19
genes
differences
methylated
differential
hippocampus.
Among
these
genes,
determined
total
nine
expressed
may
be
closely
occurrence
induced
by
exposures.
further
found
alkB
homolog
5
(ALKBH5),
but
not
methyltransferase‐like
3
(METTL3)
Wilms
tumor
1‐associated
protein
(WTAP),
were
increased
And
IOX1,
an
inhibitor
ALKBH5,
significantly
improved
memory
defects
reduced
neuronal
damage
The
current
study
revealed
role
m6A‐related
regulators
sevoflurane‐induced
cognitive
impairment,
which
might
provide
novel
insight
into
identifying
biomarkers
therapeutic
strategies
anesthetic‐induced
neurotoxicity.
Frontiers in Cell and Developmental Biology,
Год журнала:
2024,
Номер
12
Опубликована: Авг. 16, 2024
ALKBH5
is
one
of
the
demethylases
involved
in
regulation
RNA
m6A
modification.
In
addition
to
its
role
dynamic
modification,
has
been
found
play
important
roles
various
tissues
fibrosis
processes
recent
years.
However,
mechanisms
and
effects
have
reported
inconsistently.
Multiple
cell
types,
including
parenchymal
cells,
immune
cells
(neutrophils
T
cells),
macrophages,
endothelial
fibroblasts,
stages
fibrosis.
Therefore,
this
review
analyzes
by
which
regulates
these
impact
on
their
functions,
outcomes
Furthermore,
summarizes
fibrotic
diseases
such
as
pulmonary
fibrosis,
liver
cardiac
renal
discusses
inhibitors
that
discovered
date,
exploring
potential
a
clinical
target
for
Investigative Ophthalmology & Visual Science,
Год журнала:
2024,
Номер
65(12), С. 34 - 34
Опубликована: Окт. 23, 2024
Purpose:
This
study
aims
to
explore
the
regulatory
role
and
potential
mechanisms
of
ALKBH5-mediated
N6-methyladenosine
(m6A)
demethylation
modification
in
corneal
neovascularization
(CNV).
Methods:
A
mouse
CNV
model
was
established
through
alkali
burns.
Total
m6A
levels
were
measured
using
an
RNA
methylation
quantification
kit.
The
mRNA
expression
candidate
m6A-related
enzymes
quantified
by
quantitative
RT–PCR.
Small
interfering
targeting
ALKBH5
injected
subconjunctivally
into
alkali-burned
mice.
area,
epithelial
thickness,
pathological
changes
evaluated.
Protein
detected
western
blot
immunofluorescence.
Human
umbilical
vein
endothelial
cells
(HUVECs)
treated
with
IL-6.
Plasmid
transfection
knocked
down
or
overexpressed
FOXM1
IL-6–induced
HUVECs.
assays
CCK8,
wound
healing,
tube
formation
evaluated
cell
proliferation,
migration,
abilities,
respectively.
dual-luciferase
assay
examined
binding
between
FOXM1.
Methylated
immunoprecipitation–qPCR
Results:
Significant
observed
on
seventh
day.
reduced,
increased
corneas
knockdown
alleviated
inflammation
countered
promotion
depletion
decreased
VEGFA
CD31
both
vivo
vitro.
HUVECs
elevated
while
reducing
its
protein
expression.
Notably,
overexpression
can
reverse
effects.
Conclusions:
modulates
demethylation,
influencing
progression
highlighting
as
a
therapeutic
target.
