Nature Cell Biology,
Journal Year:
2023,
Volume and Issue:
25(9), P. 1359 - 1368
Published: Aug. 28, 2023
N6-methyladenosine
(m6A)
methylation
can
be
deposited
on
chromatin-associated
RNAs
(caRNAs)
by
the
RNA
methyltransferase
complex
(MTC)
to
regulate
chromatin
state
and
transcription.
However,
mechanism
which
MTC
is
recruited
distinct
genomic
loci
remains
elusive.
Here
we
identify
RBFOX2,
a
well-studied
RNA-binding
protein,
as
factor
that
preferentially
recognizes
m6A
caRNAs.
RBFOX2
recruit
RBM15,
an
component,
facilitate
of
promoter-associated
RNAs.
RBM15
also
physically
interacts
with
YTHDC1
recruits
polycomb
repressive
2
(PRC2)
RBFOX2-bound
for
silencing
transcription
suppression.
Furthermore,
found
this
RBFOX2/m6A/RBM15/YTHDC1/PRC2
axis
plays
critical
role
in
myeloid
leukaemia.
Downregulation
notably
inhibits
survival/proliferation
acute
leukaemia
cells
promotes
their
differentiation.
required
self-renewal
stem/initiation
maintenance.
Our
study
presents
pathway
recruitment
deposition
caRNAs,
resulting
locus-selective
regulation,
has
potential
therapeutic
implications
Signal Transduction and Targeted Therapy,
Journal Year:
2022,
Volume and Issue:
7(1)
Published: Nov. 7, 2022
Abstract
Aging
is
accompanied
by
the
decline
of
organismal
functions
and
a
series
prominent
hallmarks,
including
genetic
epigenetic
alterations.
These
aging-associated
changes
include
DNA
methylation,
histone
modification,
chromatin
remodeling,
non-coding
RNA
(ncRNA)
regulation,
all
which
participate
in
regulation
aging
process,
hence
contribute
to
aging-related
diseases.
Therefore,
understanding
mechanisms
will
provide
new
avenues
develop
strategies
delay
aging.
Indeed,
interventions
based
on
manipulating
have
led
alleviation
or
extension
lifespan
animal
models.
Small
molecule-based
therapies
reprogramming
that
enable
rejuvenation
been
developed
for
ameliorating
reversing
conditions.
In
addition,
adopting
health-promoting
activities,
such
as
caloric
restriction,
exercise,
calibrating
circadian
rhythm,
has
demonstrated
Furthermore,
various
clinical
trials
intervention
are
ongoing,
providing
more
evidence
safety
efficacy
these
therapies.
Here,
we
review
recent
work
outline
advances
age-associated
A
better
critical
roles
epigenetics
process
lead
prevention
human
therapy
Trends in Genetics,
Journal Year:
2021,
Volume and Issue:
38(2), P. 182 - 193
Published: July 19, 2021
Chemical
modifications
on
histones,
DNA,
and
RNA
robustly
impact
gene
regulation.
Installation
of
the
modification
m6A
leads
to
altered
mRNA
stability
translation.
Emerging
data
suggest
that
perturbations
in
feedback
epigenetic
checkpoints
vice
versa.RNA
methylation
intracisternal
A
particle,
a
type
repetitive
element,
is
required
for
proper
heterochromatin
formation
maintain
genome
integrity.Loss
mouse
embryonic
stem
cells
enhances
chromatin-associated
RNAs,
leading
more-open
chromatin
active
transcription.m6A
destabilizes
transcripts
encode
histone-modifying
enzymes
complexes,
including
KDM6B,
CBP,
P300.The
histone
elongation
mark
H3K36me3
guides
deposition.Xist-mediated
silencing
X
chromosome
requires
deposition
recognition
by
reader
proteins.m6A
influence
extends
beyond
stability,
investigation
functional
effects
biogenesis
should
be
considered
physiological
mechanistic
studies.
Epigenetic
occur
genomic
DNA
histones
expression.
More
recently,
discovery
undergoes
similar
chemical
powerfully
transcript
turnover
translation
adds
another
layer
dynamic
Central
precise
synchronized
regulation
expression
intricate
crosstalk
between
multiple
involved
biosynthesis
processing.
There
are
more
than
100
internal
mammalian
cells.
The
most
common
N6-methyladenosine
(m6A)
methylation.
Although
established
dynamics
efficiency,
rapidly
accumulating
evidence
shows
significant
histone/DNA
mechanisms.
These
interactions
specify
transcriptional
outputs,
translation,
recruitment
modifiers,
as
well
deployment
methyltransferase
complex
(MTC)
at
target
sites.
In
this
review,
we
dissect
m6A-orchestrated
circuits
regulate
activity
regulatory
such
long
noncoding
(lnc)RNA
chromosome-associated
RNA.
Collectively,
body
suggests
acts
versatile
checkpoint
can
couple
different
layers
with
one
another.
