Frontiers in Immunology,
Год журнала:
2023,
Номер
14
Опубликована: Окт. 17, 2023
The
post-transcriptional
RNA
modifications
impact
the
dynamic
regulation
of
gene
expression
in
diverse
biological
and
physiological
processes.
Host
play
an
indispensable
role
regulating
innate
immune
responses
against
virus
infection
mammals.
Meanwhile,
viral
RNAs
can
be
deposited
with
to
interfere
host
responses.
N
6
-methyladenosine
(m
A)
has
boosted
recent
emergence
epigenetics,
due
its
high
abundance
a
transcriptome-wide
widespread
distribution
mammalian
cells,
proven
antiviral
immunity.
However,
other
types
are
also
involved
responses,
functional
roles
these
non-m
A
have
not
been
comprehensively
summarized.
In
this
Review
,
we
conclude
regulatory
2’-
O
-methylation
(Nm),
5-methylcytidine
5
C),
adenosine-inosine
editing
(A-to-I
editing),
pseudouridine
(Ψ),
1
A),
7
-methylguanosine
G),
,2’-
-dimethyladenosine
Am),
4
-acetylcytidine
(ac
C)
We
provide
systematic
introduction
biogenesis
functions
RNA,
during
virus-host
interactions,
emphasizing
modification
regulators
Furthermore,
discussed
research
progress
development
drugs
through
modifications.
Collectively,
conveys
knowledge
inspiration
researchers
multiple
disciplines,
highlighting
challenges
future
directions
epitranscriptome,
immunology,
virology.
Cancer Communications,
Год журнала:
2024,
Номер
44(9), С. 1018 - 1041
Опубликована: Июль 19, 2024
Abstract
Background
N4‐acetylcytidine
(ac4C)
represents
a
novel
messenger
RNA
(mRNA)
modification,
and
its
associated
acetyltransferase
N‐acetyltransferase
10
(NAT10)
plays
crucial
role
in
the
initiation
progression
of
tumors
by
regulating
mRNA
functionality.
However,
hepatocellular
carcinoma
(HCC)
development
prognosis
is
largely
unknown.
This
study
aimed
to
elucidate
NAT10‐mediated
ac4C
HCC
provide
promising
therapeutic
approach.
Methods
The
levels
were
evaluated
dot
blot
ultra‐performance
liquid
chromatography‐tandem
mass
spectrometry
with
harvested
tissues.
expression
NAT10
was
investigated
using
quantitative
real‐time
polymerase
chain
reaction,
western
blotting,
immunohistochemical
staining
across
91
cohorts
patients.
To
explore
underlying
mechanisms
NAT10‐ac4C
HCC,
we
employed
comprehensive
approach
integrating
acetylated
immunoprecipitation
sequencing,
sequencing
ribosome
profiling
analyses,
along
immunoprecipitation,
pull‐down,
spectrometry,
site‐specific
mutation
analyses.
drug
affinity
responsive
targets
stability,
cellular
thermal
shift
assay,
surface
plasmon
resonance
assays
performed
assess
specific
binding
Panobinostat.
Furthermore,
efficacy
targeting
for
treatment
elucidated
through
vitro
experiments
cells
vivo
mouse
models.
Results
Our
investigation
revealed
significant
increase
both
level
HCC.
Notably,
elevated
poor
outcomes
Functionally,
silencing
suppressed
proliferation
metastasis
vivo.
Mechanistically,
stimulates
modification
within
coding
sequence
(CDS)
high
mobility
group
protein
B2
(HMGB2),
which
subsequently
enhances
HMGB2
translation
facilitating
eukaryotic
elongation
factor
2
(eEF2)
sites
on
mRNA's
CDS.
Additionally,
high‐throughput
compound
library
screening
Panobinostat
as
potent
inhibitor
modification.
inhibition
significantly
attenuated
growth
Conclusions
identified
oncogenic
epi‐transcriptome
axis
involving
NAT10‐ac4C/eEF2‐HMGB2,
pivotal
metastasis.
validates
potential
this
treatment.
In
recent
years,
concerted
efforts
to
map
and
understand
epitranscriptomic
modifications
in
mRNA
have
unveiled
new
complexities
the
regulation
of
gene
expression.
These
studies
cumulatively
point
diverse
functions
metabolism,
spanning
pre-mRNA
processing,
degradation,
translation.
However,
this
emerging
landscape
is
not
without
its
intricacies
sources
discrepancies.
Disparities
detection
methodologies,
divergent
interpretations
functional
outcomes,
complex
nature
biological
systems
across
different
cell
types
pose
significant
challenges.
With
a
focus
N4-acetylcytidine
(ac4C),
review
endeavors
unravel
conflicting
narratives
by
examining
technological,
biological,
methodological
factors
that
contributed
discrepancies
thwarted
research
progress.
Our
goal
mitigate
inconsistencies
establish
unified
model
elucidate
contribution
ac4C
metabolism
cellular
equilibrium.
Heliyon,
Год журнала:
2024,
Номер
10(2), С. e24573 - e24573
Опубликована: Янв. 1, 2024
Ischemia-reperfusion
injury
(IRI)
is
a
significant
contributor
to
acute
kidney
(AKI)
and
associated
with
substantial
morbidity
mortality
rates.
In
this
study,
we
aimed
investigate
the
role
of
NAT10
its
ac4C
RNA
modification
in
IRI-induced
renal
injury.
Our
findings
revealed
that
both
expression
level
kidneys
were
elevated
IRI
group
compared
sham
group.
Functionally,
observed
inhibition
activity
Remodelin
or
specific
knockout
led
attenuation
Furthermore,
vitro
experiments
demonstrated
markedly
suppressed
global
modification,
providing
protection
against
hypoxia/reoxygenation-induced
tubular
epithelial
cell
ferroptosis.
Mechanistically,
our
study
uncovered
promoted
NCOA4
mRNA,
thereby
enhancing
stability
contributing
ferroptosis
cells
(TECs).
These
underscore
potential
as
promising
therapeutic
targets
for
treatment
AKI.
Overall,
sheds
light
on
critical
involvement
pathogenesis
injury,
offering
valuable
insights
development
novel
AKI
strategies.
Annals of the Rheumatic Diseases,
Год журнала:
2024,
Номер
unknown, С. ard - 225343
Опубликована: Май 8, 2024
Recent
studies
indicate
that
N-acetyltransferase
10
(NAT10)-mediated
ac4C
modification
plays
unique
roles
in
tumour
metastasis
and
immune
infiltration.
This
study
aimed
to
uncover
the
role
of
NAT10-mediated
fibroblast-like
synoviocytes
(FLSs)
functions
synovial
cell
infiltration
rheumatoid
arthritis
(RA).
Experimental & Molecular Medicine,
Год журнала:
2024,
Номер
56(9), С. 1909 - 1920
Опубликована: Сен. 2, 2024
Functional
variations
in
coding
and
noncoding
RNAs
are
crucial
tumorigenesis,
with
cancer-specific
alterations
often
resulting
from
chemical
modifications
posttranscriptional
processes
mediated
by
enzymes.
These
RNA
have
been
linked
to
tumor
cell
proliferation,
growth,
metastasis,
drug
resistance
valuable
for
identifying
diagnostic
or
prognostic
cancer
biomarkers.
The
diversity
of
modifications,
such
as
splicing,
polyadenylation,
methylation,
editing,
is
particularly
significant
due
their
prevalence
impact
on
progression.
Additionally,
other
including
acetylation,
circularization,
miRNA
isomerization,
pseudouridination,
recognized
key
contributors
development.
Understanding
the
mechanisms
underlying
these
can
enhance
our
knowledge
biology
facilitate
development
innovative
therapeutic
strategies.
Targeting
regulatory
enzymes
may
pave
way
novel
RNA-based
therapies,
enabling
tailored
interventions
specific
subtypes.
This
review
provides
a
comprehensive
overview
roles
various
progression
highlights
recent
advancements
applications.
Abstract
RNA‐modifying
proteins,
classified
as
“writers,”
“erasers,”
and
“readers,”
dynamically
modulate
RNA
by
adding,
removing,
or
interpreting
chemical
groups,
thereby
influencing
stability,
functionality,
interactions.
To
date,
over
170
distinct
modifications
more
than
100
enzymes
have
been
identified,
with
ongoing
research
expanding
these
numbers.
Although
significant
progress
has
made
in
understanding
modification,
the
regulatory
mechanisms
that
govern
proteins
themselves
remain
insufficiently
explored.
Post‐translational
(PTMs)
such
phosphorylation,
ubiquitination,
acetylation
are
crucial
modulating
function
behavior
of
proteins.
However,
full
extent
PTM
influence
on
their
role
disease
development
remains
to
be
fully
elucidated.
This
review
addresses
gaps
offering
a
comprehensive
analysis
roles
PTMs
play
regulating
Mechanistic
insights
provided
into
how
alter
biological
processes,
contribute
cellular
function,
drive
progression.
In
addition,
current
landscape
is
examined,
highlighting
therapeutic
potential
targeting
for
precision
medicine.
By
advancing
networks,
this
seeks
facilitate
effective
strategies
inspire
future
critical
area
Abstract
N4‐acetylcytidine
(ac4C)
modification
is
a
crucial
RNA
widely
present
in
eukaryotic
RNA.
Previous
studies
have
demonstrated
that
ac4C
plays
pivotal
role
viral
infections.
Despite
numerous
highlighting
the
strong
correlation
between
and
cancer
progression,
its
detailed
roles
molecular
mechanisms
normal
physiological
processes
progression
remain
incompletely
understood.
This
review
first
outlines
key
regulatory
enzyme
mediating
modification,
N‐acetyltransferase
10
(NAT10),
including
critical
regulating
stability,
transcriptional
efficiency,
translational
fidelity.
Additionally,
it
systematically
summarizes
essential
functions
of
biological
processes,
stem
cell
fate
determination,
spermatogenesis
oogenesis,
embryonic
development,
cellular
senescence,
bone
remodeling.
Furthermore,
this
delves
into
central
malignant
proliferation,
cycle
arrest,
EMT,
drug
resistance,
death,
metabolism,
tumor
immunotherapy.
It
also
emphasizes
potential
NAT10
as
prognostic
biomarker
therapeutic
target
for
disease
treatment.
In
summary,
clarifies
multifaceted
both
health
explores
NAT10‐targeted
therapies
with
aim
advancing
research
improving
patient
outcomes.
Scientific Reports,
Год журнала:
2025,
Номер
15(1)
Опубликована: Янв. 6, 2025
The
pathogenesis
of
metabolic
dysfunction-associated
steatotic
liver
disease
(MASLD)
remains
unclear
due
to
the
complexity
its
etiology.
emerging
field
epitranscriptome
has
shown
significant
promise
in
advancing
understanding
and
developing
new
therapeutic
approaches.
Recent
research
demonstrated
that
N4-acetylcytosine
(ac4C),
an
RNA
modification
within
epitranscriptome,
is
implicated
progression
various
diseases.
However,
role
ac4C
MASLD
unexplored.
Herein,
we
performed
acRIP-ac4c-seq
RNA-seq
analysis
free
fatty
acids-induced
model
cells,
identifying
2128
differentially
acetylated
sites,
with
1031
hyperacetylated
1097
hypoacetylated
peaks
cells.
Functional
enrichments
showed
modified
genes
were
significantly
involved
processes
related
MASLD,
such
as
nuclear
transport
MAP
kinase
(MAPK)
signaling
pathway.
We
also
identified
341
expressed
(DEGs),
including
61
lncRNAs
280
mRNAs,
between
control
Bioinformatics
DEGs
enriched
long-chain
acid
biosynthetic
process.
Notably,
118
exhibited
changes
both
expression
levels
Among
these
proteins,
JUN,
caveolin-1
(CAV1),
synthase
(FASN),
heterogeneous
ribonucleoprotein
A1
(hnRNPA1)
core
proteins
through
protein–protein
interaction
(PPI)
network
using
cytoscape
software.
Collectively,
our
findings
establish
a
positive
correlation
suggest
may
serve
target
for
MASLD.
