Cell Communication and Signaling,
Год журнала:
2022,
Номер
20(1)
Опубликована: Сен. 9, 2022
Abstract
N6-methyl-adenosine
(m
6
A)
is
the
most
prevalent
modification
on
mRNAs
and
long
noncoding
RNAs
(lnRNAs)
in
higher
eukaryotes.
Modulation
of
m
A
relies
writers,
erasers
readers.
contributes
to
diverse
fundamental
biological
functions
at
molecular,
cellular,
physiological
levels.
The
dysregulation
has
been
implicated
various
human
diseases.
Thus,
now
become
a
research
hotspot
for
its
potential
therapeutic
applications
treatment
cancers
immune
system
essential
provide
defense
against
infections
cancers.
This
review
summarizes
current
knowledge
about
roles
regulating
cell
responses.
Signal Transduction and Targeted Therapy,
Год журнала:
2022,
Номер
7(1)
Опубликована: Сен. 22, 2022
RNA
modifications
have
become
hot
topics
recently.
By
influencing
processes,
including
generation,
transportation,
function,
and
metabolization,
they
act
as
critical
regulators
of
cell
biology.
The
immune
abnormality
in
human
diseases
is
also
a
research
focus
progressing
rapidly
these
years.
Studies
demonstrated
that
participate
the
multiple
biological
processes
cells,
development,
differentiation,
activation,
migration,
polarization,
thereby
modulating
responses
are
involved
some
related
diseases.
In
this
review,
we
present
existing
knowledge
functions
underlying
mechanisms
modifications,
N6-methyladenosine
(m6A),
5-methylcytosine
(m5C),
N1-methyladenosine
(m1A),
N7-methylguanosine
(m7G),
N4-acetylcytosine
(ac4C),
pseudouridine
(Ψ),
uridylation,
adenosine-to-inosine
(A-to-I)
editing,
summarize
their
roles
Via
regulating
can
pathogenesis
diseases,
such
cancers,
infection,
inflammatory
autoimmune
We
further
highlight
challenges
future
directions
based
on
knowledge.
All
all,
review
will
provide
helpful
well
novel
ideas
for
researchers
area.
Genes & Development,
Год журнала:
2021,
Номер
35(13-14), С. 1005 - 1019
Опубликована: Июнь 24, 2021
N
6
-methyladenosine
(m
A)
is
an
abundant
internal
RNA
modification,
influencing
transcript
fate
and
function
in
uninfected
virus-infected
cells.
Installation
of
m
A
by
the
nuclear
methyltransferase
METTL3
occurs
cotranscriptionally;
however,
genomes
some
cytoplasmic
viruses
are
also
A-modified.
How
cellular
modification
machinery
impacts
coronavirus
replication,
which
exclusively
cytoplasm,
unknown.
Here
we
show
that
replication
SARS-CoV-2,
agent
responsible
for
COVID-19
pandemic,
a
seasonal
human
β-coronavirus
HCoV-OC43,
can
be
suppressed
depletion
or
reader
proteins
YTHDF1
YTHDF3
highly
specific
small
molecule
inhibitor.
Reduction
infectious
titer
correlates
with
decreased
synthesis
viral
RNAs
essential
nucleocapsid
(N)
protein.
Sites
on
genomic
subgenomic
both
were
mapped
methylated
immunoprecipitation
sequencing
(meRIP-seq).
Levels
host
factors
involved
installation,
removal,
recognition
unchanged
HCoV-OC43
infection;
localization
readers
YTHDF2
increased.
This
establishes
A-modified
pathway
components
control
replication.
Moreover,
it
illustrates
therapeutic
potential
targeting
to
restrict
reproduction.
Chemical Reviews,
Год журнала:
2024,
Номер
124(3), С. 929 - 1033
Опубликована: Янв. 29, 2024
RNA-based
therapies
have
catalyzed
a
revolutionary
transformation
in
the
biomedical
landscape,
offering
unprecedented
potential
disease
prevention
and
treatment.
However,
despite
their
remarkable
achievements,
these
encounter
substantial
challenges
including
low
stability,
susceptibility
to
degradation
by
nucleases,
prominent
negative
charge,
thereby
hindering
further
development.
Chemically
modified
platforms
emerged
as
strategic
innovation,
focusing
on
precise
alterations
either
RNA
moieties
or
associated
delivery
vectors.
This
comprehensive
review
delves
into
platforms,
underscoring
significance
augmenting
performance
translational
prospects
of
therapeutics.
It
encompasses
an
in-depth
analysis
various
chemically
that
been
instrumental
propelling
therapeutics
toward
clinical
utility.
Moreover,
scrutinizes
rationale
behind
diverse
chemical
modification
techniques
aiming
at
optimizing
therapeutic
efficacy
molecules,
facilitating
robust
management.
Recent
empirical
studies
corroborating
enhancement
through
modifications
are
highlighted.
Conclusively,
we
offer
profound
insights
transformative
impact
drugs
delineates
prospective
trajectories
for
future
development
integration.
Annual Review of Immunology,
Год журнала:
2023,
Номер
41(1), С. 73 - 98
Опубликована: Апрель 26, 2023
Characterization
of
RNA
modifications
has
identified
their
distribution
features
and
molecular
functions.
Dynamic
changes
in
modification
on
various
forms
are
essential
for
the
development
function
immune
system.
In
this
review,
we
discuss
value
innovative
profiling
technologies
to
uncover
these
diverse,
dynamic
cells
within
healthy
diseased
contexts.
Further,
explore
our
current
understanding
mechanisms
whereby
aberrant
modulate
milieu
tumor
microenvironment
point
out
outstanding
research
questions.
Nature Communications,
Год журнала:
2022,
Номер
13(1)
Опубликована: Окт. 26, 2022
Abstract
The
methyltransferase
like
3
(METTL3)
has
been
generally
recognized
as
a
nuclear
protein
bearing
oncogenic
properties.
We
find
predominantly
cytoplasmic
METTL3
expression
inversely
correlates
with
node
metastasis
in
human
cancers.
It
remains
unclear
if
is
functionally
distinct
from
cytosolic
driving
tumorigenesis
and,
any,
how
tumor
cells
sense
insults
to
coordinate
functions
within
these
intracellular
compartments.
Here,
we
report
an
acetylation-dependent
regulation
of
localization
that
impacts
on
metastatic
dissemination.
identify
IL-6-dependent
positive
feedback
axis
facilitate
functions,
eliciting
breast
cancer
metastasis.
IL-6,
whose
mRNA
transcript
subjected
METTL3-mediated
m
6
A
modification,
promotes
deacetylation
and
translocation,
thereby
inducing
global
abundance.
This
deacetylation-mediated
shift
can
be
counterbalanced
by
SIRT1
inhibition,
process
further
enforced
aspirin
treatment,
leading
ablated
lung
via
impaired
methylation.
Intriguingly,
acetylation-mimetic
mutant
reconstitution
results
enhanced
translation
compromised
potential.
Our
study
identifies
regulatory
mechanism
determining
the
subcellular
METTL3,
which
may
provide
mechanistic
clues
for
developing
therapeutic
strategies
combat
Frontiers in Pharmacology,
Год журнала:
2022,
Номер
13
Опубликована: Апрель 27, 2022
N6-Methyladenosine
(m6A)
is
the
most
prevalent
mRNA
modification
in
mammalian
cells
that
mainly
catalyzed
by
methyltransferase
complex
of
methyltransferase-like
3
and
14
(METTL3-METTL14).
Many
lines
evidence
suggest
METTL3
plays
important
roles
several
diseases
such
as
cancers
viral
infection.
In
present
study,
1,042
natural
products
from
commercially
available
sources
were
chosen
to
establish
a
screening
library,
docking-based
high-throughput
was
performed
discover
potential
inhibitors.
The
selected
compounds
then
further
validated
an
vitro
inhibition
assay
which
m6A
content
determined
LC-MS/MS.
A
cellular
methylation
determine
inhibitory
activity
compound.
CCK-8
applied
evaluate
effects
compound
on
tumor
cell
viability.
Additionally,
binding
mode
analysis,
molecular
dynamics
(MD)
simulation,
free
energy
analysis
study
process
characteristics
inhibitor
binding.
Finally,
quercetin
identified
with
IC50
value
2.73
μM.
showed
decreased
level
dose-dependent
manner
MIA
PaCa-2
pancreatic
cancer
cells.
efficiently
inhibited
proliferation
Huh7
cells,
values
73.51
±
11.22
μM
99.97
7.03
μM,
respectively.
Molecular
docking
studies
revealed
filled
pocket
adenosine
moiety
SAM
but
not
methionine
protein,
hydrogen
bonds,
hydrophobic
interactions,
pi-stacking
formed.
root
mean
square
deviation
(RMSD),
fluctuations
(RMSF),
suggested
can
bind
protein
form
stable
protein-ligand
complex.
first
identify
inhibitors
products,
thus
providing
basis
for
subsequent
research
facilitating
development
METTL3-targeting
drugs
diseases.
