Cell Death and Disease,
Journal Year:
2021,
Volume and Issue:
12(11)
Published: Oct. 23, 2021
Abstract
Proper
follicle
development
is
very
important
for
the
production
of
mature
oocytes,
which
essential
maintenance
female
fertility.
This
complex
biological
process
requires
precise
gene
regulation.
The
most
abundant
modification
mRNA,
N
6
-methyladenosine
(m
A),
involved
in
many
RNA
metabolism
processes,
including
splicing,
translation,
stability,
and
degradation.
Here,
we
report
that
m
A
plays
roles
during
oocyte
development.
Oocyte-specific
inactivation
key
methyltransferase
Mettl3
with
Gdf9
-Cre
caused
DNA
damage
accumulation
defective
development,
abnormal
ovulation.
Mechanistically,
combined
RNA-seq
methylated
immunoprecipitation
sequencing
(MeRIP-seq)
data
from
oocytes
revealed,
found
METTL3
targets
Itsn2
then
enhances
its
stability
to
influence
meiosis.
Taken
together,
our
findings
highlight
crucial
mRNA
coordination
stabilization
growth.
Journal of Hematology & Oncology,
Journal Year:
2021,
Volume and Issue:
14(1)
Published: July 27, 2021
Abstract
N6-methyladenosine
(m6A)
has
emerged
as
an
abundant
modification
throughout
the
transcriptome
with
widespread
functions
in
protein-coding
and
noncoding
RNAs.
It
affects
fates
of
modified
RNAs,
including
their
stability,
splicing,
and/or
translation,
thus
plays
important
roles
posttranscriptional
regulation.
To
date,
m6A
methyltransferases
have
been
reported
to
execute
deposition
on
distinct
RNAs
by
own
or
forming
different
complexes
additional
partner
proteins.
In
this
review,
we
summarize
function
these
regulating
key
genes
pathways
cancer
biology.
We
also
highlight
progress
use
mediating
therapy
resistance,
chemotherapy,
targeted
therapy,
immunotherapy
radiotherapy.
Finally,
discuss
current
approaches
clinical
potential
methyltransferase-targeting
strategies.
Cancer Research,
Journal Year:
2021,
Volume and Issue:
81(13), P. 3431 - 3440
Published: March 5, 2021
Abstract
RNA
N6-methyladenosine
(m6A)
modification
occurs
in
approximately
25%
of
mRNAs
at
the
transcriptome-wide
level.
m6A
is
regulated
by
methyltransferases
methyltransferase-like
3
(METTL3),
METTL14,
and
METTL16
(writers),
demethylases
FTO
ALKBH5
(erasers),
binding
proteins
YTHDC1–2,
YTHDF1–3,
IGF2BP1–3,
SND1
(readers).
These
are
frequently
upregulated
or
downregulated
human
cancer
tissues
often
associated
with
poor
patient
prognosis.
By
modulating
pre-mRNA
splicing,
mRNA
nuclear
export,
decay,
stability,
translation
oncogenic
tumor
suppressive
transcripts,
regulate
cell
proliferation,
survival,
migration,
invasion,
initiation,
progression,
metastasis,
sensitivity
to
anticancer
therapies.
Importantly,
small-molecule
activators
METTL3,
as
well
inhibitors
FTO,
ALKBH5,
IGF2BP1
have
recently
been
identified
shown
considerable
effects
when
administered
alone
combination
other
agents,
both
vitro
mouse
models
cancers.
Future
compound
screening
design
more
potent
selective
protein
expected
provide
novel
appropriate
for
clinical
trials
patients
harboring
aberrant
expression
protein–induced
resistance
therapy.
Nucleic Acids Research,
Journal Year:
2021,
Volume and Issue:
49(10), P. 5779 - 5797
Published: May 1, 2021
Abstract
Faithful
genome
integrity
maintenance
plays
an
essential
role
in
cell
survival.
Here,
we
identify
the
RNA
demethylase
ALKBH5
as
a
key
regulator
that
protects
cells
from
DNA
damage
and
apoptosis
during
reactive
oxygen
species
(ROS)-induced
stress.
We
find
ROS
significantly
induces
global
mRNA
N6-methyladenosine
(m6A)
levels
by
modulating
post-translational
modifications
(PTMs),
leading
to
rapid
efficient
induction
of
thousands
genes
involved
variety
biological
processes
including
repair.
Mechanistically,
promotes
SUMOylation
through
activating
ERK/JNK
signaling,
inhibition
m6A
activity
blocking
substrate
accessibility.
Moreover,
ERK/JNK/ALKBH5-PTMs/m6A
axis
is
activated
hematopoietic
stem/progenitor
(HSPCs)
vivo
mice,
suggesting
physiological
this
molecular
pathway
stability
HSPCs.
Together,
our
study
uncovers
mechanism
involving
PTMs
increased
protect
genomic
response
ROS.
