Translational
regulation
is
pivotal
during
preimplantation
development.
However,
how
mRNAs
are
selected
for
temporal
and
their
dynamic
utilization
fate
this
period
still
unknown.
Using
a
high-resolution
ribosome
profiling
approach,
we
analyzed
the
transcriptome,
as
well
monosome-
polysome-bound
RNAs
of
mouse
oocytes
embryos,
defining
an
unprecedented
extent
spatiotemporal
translational
landscapes
rapid
developmental
phase.
We
observed
previously
unknown
mechanisms
selectivity,
i.e.,
stage-wise
deferral
loading
monosome-bound
to
polysome
active
translation,
continuous
translation
both
monosome
at
same
stage,
priming
monosomes
after
initial
activation.
showed
that
eukaryotic
initiation
factor
Eif1ad3,
which
exclusively
translated
in
2-Cell
embryo,
required
biogenesis
post
embryonic
genome
Our
study
thus
provides
genome-wide
datasets
analyses
dynamics
accompanying
mammalian
germ
cell
development
reveals
contribution
novel
pre-implantation
Nature Biotechnology,
Journal Year:
2023,
Volume and Issue:
42(4), P. 591 - 596
Published: June 22, 2023
Abstract
Current
N
6
-methyladenosine
(m
A)
mapping
methods
need
large
amounts
of
RNA
or
are
limited
to
cultured
cells.
Through
optimized
sample
recovery
and
signal-to-noise
ratio,
we
developed
picogram-scale
m
A
immunoprecipitation
sequencing
(picoMeRIP–seq)
for
studying
in
vivo
single
cells
scarce
cell
types
using
standard
laboratory
equipment.
We
benchmark
on
titrations
poly(A)
embryonic
stem
zebrafish
zygotes,
mouse
oocytes
embryos.
Journal of Cellular and Molecular Medicine,
Journal Year:
2024,
Volume and Issue:
28(4)
Published: Feb. 1, 2024
Several
studies
have
highlighted
the
functional
indispensability
of
methyltransferase-like
3
(METTL3)
in
reproductive
system.
However,
a
review
that
comprehensively
interprets
these
and
elucidates
their
relationships
is
lacking.
Therefore,
present
work
aimed
to
investigated
functions
METTL3
system
(including
spermatogenesis,
follicle
development,
gametogenesis,
cancer,
asthenozoospermia
assisted
reproduction
failure).
This
suggests
not
only
essential
for
normal
but
also
detrimental
occurrence
disorders.
In
addition,
promising
applications
as
diagnostic
or
prognostic
biomarker
therapeutic
target
disorders
been
proposed.
Collectively,
this
provides
comprehensive
interpretations,
novel
insights,
potential
future
perspectives
on
role
regulating
system,
which
may
be
valuable
reference
researchers
clinicians.
Nature Communications,
Journal Year:
2023,
Volume and Issue:
14(1)
Published: Oct. 17, 2023
N6-methyladenosine
(m6A)
maintains
maternal
RNA
stability
in
oocytes.
One
regulator
of
m6A,
ALKBH5,
reverses
m6A
deposition
and
is
essential
metabolism.
However,
the
specific
role
ALKBH5
oocyte
maturation
remains
elusive.
Here,
we
show
that
Alkbh5
depletion
causes
a
wide
range
defects
meiosis
results
female
infertility.
Temporal
profiling
transcriptomes
revealed
striking
accumulation
Alkbh5-/-
oocytes
during
meiotic
maturation.
Analysis
dynamics
demonstrated
ALKBH5-mediated
demethylation
ensures
timely
degradation
RNAs,
which
severely
disrupted
following
depletion.
A
distinct
subset
transcripts
with
persistent
peaks
are
recognized
by
reader
IGF2BP2
thus
remain
stabilized,
resulting
impaired
clearance.
Additionally,
reducing
Alkbh5-depleted
partially
rescued
these
defects.
Overall,
this
work
identifies
as
key
determinant
quality
unveil
facilitating
removal
decay.
Human Reproduction Update,
Journal Year:
2025,
Volume and Issue:
unknown
Published: March 27, 2025
Abstract
BACKGROUND
RNA
modifications,
collectively
known
as
the
epitranscriptome,
represent
third
layer
of
gene
regulation,
influencing
expression
at
transcriptional,
post-transcriptional,
and
translational
levels.
RNA-modifying
proteins
(RMPs),
including
writers,
erasers,
readers,
are
responsible
for
depositing,
removing,
recognizing
chemical
modifications
on
molecules.
These
play
a
crucial
role
in
linking
molecular
processes
to
cellular
functions.
Over
past
few
decades,
growing
body
laboratory
evidence,
alongside
advances
sequencing
technologies,
has
uncovered
connections
between
aberrant
reproductive
disorders,
highlighting
their
emerging
roles
female
fertility.
Given
rapid
expansion
epitranscriptomic
research
reproduction,
comprehensive
review
is
needed
summarize
broader
impacts
various
rather
than
focusing
individual
alone.
OBJECTIVE
AND
RATIONALE
This
aims
elucidate
progress
understanding
biology
how
dysregulations
contribute
infertility-related
conditions,
such
polycystic
ovary
syndrome
(PCOS),
premature
ovarian
insufficiency
(POI),
endometriosis.
Special
focus
will
be
given
coding
RNAs,
particularly
those
linked
fertility
supported
by
solid
evidence.
The
ultimate
objective
explore
targeting
RNA-modification
machinery
can
lead
development
novel
therapeutic
interventions
restoring
SEARCH
METHODS
We
conducted
thorough
peer-reviewed
original
articles
reviews
published
over
two
decades
using
PubMed
search
engine.
Keywords
included
terms
related
‘N6-methyladenosine
(m6A)’,
‘N4-acetylcytidine
(ac4C)’,
‘adenosine-to-inosine
(A–I)
editing’,
combined
with
‘ovary’,
‘oocyte’,
‘embryo’.
Additional
relevant
phrases
were
also
utilized
ensure
coverage
topic.
OUTCOMES
modification
emerged
transformative
area
biology,
our
epitranscriptome
rapidly
due
significant
high-throughput
technologies.
Regulatory
correct
deposition
functional
implementation
modifications.
Knockout
animal
models
have
identified
broad,
though
still
incomplete,
list
involved
mammalian
processes.
include
prevalent
mRNA,
m6A,
well
A–I
editing,
and,
lesser
extent,
5-methylcytosine
(m5C)
ac4C.
regulatory
mechanisms
impact
functions,
folliculogenesis,
oocyte
maturation,
fertilization,
embryo
development.
Dysregulation
may
exacerbate
POI,
PCOS,
Although
clinical
investigations
early
stages,
show
great
promise
diagnostic
biomarkers
targets,
potential
improve
health
outcomes.
WIDER
IMPLICATIONS
explores
relatively
underexamined
offering
significantly
advance
biology.
It
underscores
relevance
disorders
identifies
biomarkers,
RMP-targeted
therapies,
that
could
shape
future
decision-making
personalized
treatments.
insights
clinicians
embryologists,
presenting
new
avenues
diagnosis
medicine.
REGISTRATION
NUMBER
N/A.
Journal of Biological Chemistry,
Journal Year:
2025,
Volume and Issue:
unknown, P. 108479 - 108479
Published: April 1, 2025
Mouse
embryonic
stem
cells
(ESCs)
consist
of
a
rare
population
heterogeneous
2-cell-like
(2CLCs).
These
transiently
recapitulate
the
transcriptional
and
epigenetic
features
2-cell
embryos,
serving
as
unique
model
for
studying
totipotency
acquisition
development.
Accumulating
evidence
has
demonstrated
that
transcription
factors
modifications
exert
crucial
functions
in
transition
ESCs
to
2CLCs.
However,
roles
RNA
modification
regulation
2C-like
state
remain
elusive.
Using
DUX-induced
2CLCs
system,
we
examine
N6-methyladenosine
(m6A)
landscape
transcriptome-wide,
observe
dynamic
m6A
during
DUX-driven
reprogramming.
Notably,
many
core
2C
transcripts
like
Dux
Zscan4,
are
highly
methylated.
We
identify
reader
protein
YTHDF2
critical
regulator
state.
Depletion
facilitates
robust
expressions
2C-signature
genes
ESCs-to-2CLCs
transition.
Intriguingly,
binds
subset
m6A-modified
promotes
their
decay.
further
demonstrate
suppresses
program
manner
is
dependent
on
both
DUX-ZSCAN4
molecular
circuit.
Mechanistically,
interacts
with
CNOT1,
key
component
deadenylase
complex.
Consistently,
silencing
CNOT1
upregulates
Collectively,
our
findings
reveal
novel
insights
into
epitranscriptomic
mouse
ESCs.
