bioRxiv (Cold Spring Harbor Laboratory),
Journal Year:
2024,
Volume and Issue:
unknown
Published: July 16, 2024
Abstract
Epigenetic
traits
impact
the
antitumor
function
of
CD8
T
cells,
yet
whether
and
how
RNA
methylation
programs
engage
in
cell
immunity
is
poorly
understood.
Here
we
show
that
N
6
-methyladenosine
(m
A)
reader
YTHDF2
highly
expressed
early
effector
or
effector-like
cells
partially
distributed
nucleus.
loss
exacerbates
tumor
progression
confers
unresponsiveness
to
PD-1
blockade
mice
humans.
In
addition
initiating
decay
for
mitochondrial
fitness,
can
orchestrate
chromatin
regulation
promote
polyfunctionality.
YTHDF2-mediatd
preservation
gene
transcription
arises
from
interaction
with
IKZF1/3.
Accordingly,
immunotherapy-induced
efficacy
could
be
largely
restored
YTHDF2-deficient
through
combinational
use
lenalidomide.
Moreover,
m
A
recognition
fundamental
translocation
nucleus
autoregulation
at
level.
Thus,
coordinates
epitranscriptional
transcriptional
networks
potentiate
immunity.
Highlights
expression
distribution
underpin
threshold
bona
fide
response
Canonical
YTHDF2-mRNA
pathway
alleviates
stress
exhaustion
Nuclear
sequesters
IKZF1/3-mediated
repression
safeguard
polyfunctionality
The
tumoricidal
activity
repaired
synergy
anti-PD-1
lenalidomide
Frontiers in Oncology,
Journal Year:
2025,
Volume and Issue:
15
Published: Feb. 7, 2025
The
5-methylcytosine
(m5C)
modification
is
a
crucial
epigenetic
RNA
modification,
which
involved
in
the
post-transcriptional
regulation
of
genes.
It
plays
an
important
role
various
biological
processes,
including
cell
metabolism,
growth,
apoptosis,
and
tumorigenesis.
By
affecting
proliferation,
migration,
invasion,
drug
sensitivity
tumor
cells,
m5C
methylation
vital
part
initiation
progression
tumors
closely
associated
with
poor
prognosis.
m5C-related
proteins
are
categorized
into
three
functional
groups:
methyltransferases
(m5C
writers),
demethylases
erasers),
methyl-binding
readers).
This
paper
introduces
several
common
methodologies
for
detecting
methylation;
reviews
molecular
structure
functions
readers,
ALYREF,
YBX1,
YBX2,
RAD52,
YTHDF2,
FMRP,
SRSF2.
further
summarizes
their
roles
regulatory
mechanisms
tumors,
offering
novel
targets
insights
treatment.
Non-Coding RNA,
Journal Year:
2024,
Volume and Issue:
10(1), P. 11 - 11
Published: Feb. 5, 2024
Noncoding
RNAs
(ncRNAs),
including
circular
(circRNAs)
and
N6-methyladenosine
(m6A),
have
been
shown
to
play
a
critical
role
in
the
development
of
various
diseases
obesity
metabolic
disorder-associated
fatty
liver
disease
(MAFLD).
Obesity
is
chronic
caused
by
excessive
fat
accumulation
body,
which
has
recently
become
more
prevalent
foremost
risk
factor
for
MAFLD.
Causes
may
involve
interaction
genetic,
behavioral,
social
factors.
m6A
RNA
methylation
might
add
novel
inspiration
understanding
MAFLD
with
post-transcriptional
regulation
gene
expression.
In
particular,
circRNAs,
microRNAs
(miRNAs),
be
implicated
progression
Interestingly,
modification
can
modulate
translation,
degradation,
other
functions
ncRNAs.
miRNAs/circRNAs
also
modifications
affecting
writers,
erasers,
readers.
turn,
ncRNAs
could
expression
regulators
different
ways.
However,
there
limited
evidence
on
how
these
interact
affect
promotion
diseases.
It
seems
that
occur
DNA,
RNA,
proteins
associated
several
biological
properties.
This
study
provides
mechanistic
association
diseases,
especially
Comprehension
between
contribute
treatment
tactics
Journal of Clinical Investigation,
Journal Year:
2024,
Volume and Issue:
134(14)
Published: May 16, 2024
Emerging
evidence
has
linked
the
dysregulation
of
N6-methyladenosine
(m6A)
modification
to
inflammation
and
inflammatory
diseases,
but
underlying
mechanism
still
needs
investigation.
Here,
we
found
that
high
levels
m6A
in
a
variety
hyperinflammatory
states
are
p65-dependent
because
Wilms
tumor
1–associated
protein
(WTAP),
key
component
"writer"
complex,
is
transcriptionally
regulated
by
p65,
its
overexpression
can
lead
increased
modification.
Mechanistically,
upregulated
WTAP
more
prone
phase
separation
facilitate
aggregation
writer
complex
nuclear
speckles
deposition
marks
on
active
transcripts,
thereby
accelerating
proinflammatory
response.
Further,
myeloid
deficiency
attenuates
severity
LPS-induced
sepsis
DSS-induced
IBD.
Thus,
effect
general
risk-increasing
mechanism,
interrupting
assembly
reduce
global
targeting
may
be
potential
promising
therapeutic
strategy
for
alleviating
hyperinflammation.
Frontiers in Immunology,
Journal Year:
2024,
Volume and Issue:
15
Published: Sept. 20, 2024
RNA
modifications
are
epigenetic
changes
that
alter
the
structure
and
function
of
molecules,
playing
a
crucial
role
in
onset,
progression,
treatment
cancer.
Immune
checkpoint
inhibitor
(ICI)
therapies,
particularly
PD-1
blockade
anti-CTLA-4
treatments,
have
changed
landscape
virous
cancers,
showing
great
potential
different
cancer
patients,
but
sensitivity
to
these
therapies
is
limited
certain
individuals.
This
review
offers
comprehensive
survey
functions
therapeutic
implications
four
principal
modifications,
highlighting
significance
m6A
realms
immune
cells
tumor
immunotherapy.
starts
by
providing
foundational
summary
roles
assume
within
cell
community,
focusing
on
T
cells,
NK
macrophages,
dendritic
cells.
We
then
discuss
how
influence
intricate
regulatory
mechanisms
governing
expression,
modulation
ICI
efficacy,
prediction
outcomes,
drug
targeting
genes
regulated
modifications.
Finally,
we
explore
gene
editing,
vaccines,
adoptive
offering
valuable
insights
into
use
iScience,
Journal Year:
2024,
Volume and Issue:
27(8), P. 110524 - 110524
Published: July 20, 2024
RNA
methylation
has
emerged
as
a
dynamic
regulatory
mechanism
that
impacts
gene
expression
and
protein
synthesis.
Among
the
known
modifications,
N6-methyladenosine
(m