International Journal of Molecular Sciences,
Journal Year:
2025,
Volume and Issue:
26(7), P. 3310 - 3310
Published: April 2, 2025
For
nearly
three
decades,
interspecies
somatic
cell
nuclear
transfer
(iSCNT)
has
been
explored
as
a
potential
tool
for
cloning,
regenerative
medicine,
and
wildlife
conservation.
However,
developmental
inefficiencies
remain
major
challenge,
largely
due
to
persistent
barriers
in
nucleocytoplasmic
transport,
mitonuclear
communication,
epigenome
crosstalk.
This
review
synthesized
peer-reviewed
English
articles
from
PubMed,
Web
of
Science,
Scopus,
spanning
using
relevant
keywords
explore
the
molecular
mechanisms
underlying
iSCNT
improvement
strategies.
We
highlight
recent
findings
deepening
understanding
iSCNT,
emphasizing
their
interconnected
complexities,
including
following:
(1)
incompatibility
may
disrupt
pore
complex
(NPC)
assembly
maturation,
impairing
transport
essential
transcription
factors
(TFs),
embryonic
genome
activation
(EGA),
reprogramming;
(2)
could
lead
mitochondrial
DNA
(nDNA-mtDNA)
mismatches,
affecting
electron
chain
(ETC)
assembly,
oxidative
phosphorylation,
energy
metabolism;
(3)
these
interrelated
incompatibilities
can
further
influence
epigenetic
regulation,
potentially
leading
incomplete
reprogramming
embryos.
Addressing
challenges
requires
multifaceted,
species-specific
approach
that
balances
multiple
rather
than
isolating
single
factor.
Gaining
insight
into
interactions
between
donor
nucleus
recipient
cytoplast,
coupled
with
optimizing
strategies
tailored
specific
pairings,
significantly
enhance
efficiency,
ultimately
transforming
experimental
breakthroughs
real-world
applications
reproductive
biotechnology,
species
Nature,
Journal Year:
2023,
Volume and Issue:
617(7959), P. 162 - 169
Published: April 26, 2023
Abstract
The
approximately
120
MDa
mammalian
nuclear
pore
complex
(NPC)
acts
as
a
gatekeeper
for
the
transport
between
nucleus
and
cytosol
1
.
central
channel
of
NPC
is
filled
with
hundreds
intrinsically
disordered
proteins
(IDPs)
called
FG-nucleoporins
(FG-NUPs)
2,3
Although
structure
scaffold
has
been
resolved
in
remarkable
detail,
actual
machinery
built
up
by
FG-NUPs—about
50
MDa—is
depicted
an
60-nm
hole
even
highly
tomograms
and/or
structures
computed
artificial
intelligence
4–11
Here
we
directly
probed
conformations
vital
FG-NUP98
inside
NPCs
live
cells
permeabilized
intact
using
synthetic
biology-enabled
site-specific
small-molecule
labelling
approach
paired
time-resolved
fluorescence
microscopy.
Single
cell
measurements
distance
distribution
segments
combined
coarse-grained
molecular
simulations
allowed
us
to
map
uncharted
environment
nanosized
channel.
We
determined
that
provides—in
terminology
Flory
polymer
theory
12
—a
‘good
solvent’
environment.
This
enables
FG
domain
adopt
expanded
thus
control
cytoplasm.
With
more
than
30%
proteome
being
formed
from
IDPs,
our
study
opens
window
into
resolving
disorder–function
relationships
IDPs
situ,
which
are
important
various
processes,
such
cellular
signalling,
phase
separation,
ageing
viral
entry.
Cell,
Journal Year:
2024,
Volume and Issue:
187(19), P. 5267 - 5281.e13
Published: Aug. 9, 2024
The
nuclear
pore
complex
(NPC)
is
the
sole
mediator
of
nucleocytoplasmic
transport.
Despite
great
advances
in
understanding
its
conserved
core
architecture,
peripheral
regions
can
exhibit
considerable
variation
within
and
between
species.
One
such
structure
cage-like
basket.
crucial
roles
mRNA
surveillance
chromatin
organization,
an
architectural
has
remained
elusive.
Using
in-cell
cryo-electron
tomography
subtomogram
analysis,
we
explored
NPC's
structural
variations
basket
across
fungi
(yeast;
S.
cerevisiae),
mammals
(mouse;
M.
musculus),
protozoa
(T.
gondii).
integrative
modeling,
computed
a
model
yeast
that
revealed
how
hub
nucleoporins
(Nups)
ring
binds
to
basket-forming
Mlp/Tpr
proteins:
coiled-coil
domains
form
struts
basket,
while
their
unstructured
termini
constitute
distal
densities,
which
potentially
serve
as
docking
site
for
preprocessing
before
Cells,
Journal Year:
2022,
Volume and Issue:
11(9), P. 1456 - 1456
Published: April 25, 2022
Nuclear
pore
complexes
(NPCs)
are
the
only
transport
channels
that
cross
nuclear
envelope.
Constructed
from
~500–1000
nucleoporin
proteins
each,
they
among
largest
macromolecular
assemblies
in
eukaryotic
cells.
Thanks
to
advances
structural
analysis
approaches,
construction
principles
and
architecture
of
NPC
have
recently
been
revealed
at
submolecular
resolution.
Although
overall
structure
inventory
nucleoporins
conserved,
NPCs
exhibit
significant
compositional
functional
plasticity
even
within
single
cells
surprising
variability
their
assembly
pathways.
Once
assembled,
remain
seemingly
unexchangeable
post-mitotic
There
a
number
as
yet
unresolved
questions
about
how
versatility
composition
is
established,
monitor
state
or
could
be
renewed.
Here,
we
review
current
progress
our
understanding
key
aspects
lifecycle.
Nucleus,
Journal Year:
2024,
Volume and Issue:
15(1)
Published: Jan. 18, 2024
The
nuclear
envelope
(NE)
regulates
functions,
including
transcription,
nucleocytoplasmic
transport,
and
protein
quality
control.
While
the
outer
membrane
of
NE
is
directly
continuous
with
endoplasmic
reticulum
(ER),
has
an
overall
distinct
composition
from
ER,
which
crucial
for
its
functions.
During
open
mitosis
in
higher
eukaryotes,
disassembles
during
mitotic
entry
then
reforms
as
a
functional
territory
at
end
to
reestablish
compartmentalization.
In
this
review,
we
examine
known
mechanisms
by
reconstitutes
ER
ER–NE
endomembrane
system
mitosis.
Furthermore,
based
on
recent
findings
indicating
that
possesses
unique
lipid
metabolism
control
those
explore
maintenance
identity
homeostasis
interphase.
We
also
highlight
potential
significance
junctions
between
NE.
Nucleus,
Journal Year:
2024,
Volume and Issue:
15(1)
Published: Feb. 21, 2024
The
separation
of
genetic
material
from
bulk
cytoplasm
has
enabled
the
evolution
increasingly
complex
organisms,
allowing
for
development
sophisticated
forms
life.
However,
this
complexity
created
new
categories
dysfunction,
including
those
related
to
movement
between
cellular
compartments.
In
eukaryotic
cells,
nucleocytoplasmic
trafficking
is
a
fundamental
biological
process,
and
cumulative
disruptions
nuclear
integrity
transport
are
detrimental
cell
survival.
This
particularly
true
in
post-mitotic
neurons,
where
pore
injury
errors
strongly
associated
with
neurodegenerative
disease.
review,
we
summarize
current
understanding
biology
physiological
pathological
contexts
discuss
potential
therapeutic
approaches
addressing
dysfunctional
transport.
bioRxiv (Cold Spring Harbor Laboratory),
Journal Year:
2024,
Volume and Issue:
unknown
Published: Feb. 5, 2024
Abstract
Nuclear
pore
complexes
(NPCs)
constitute
giant
channels
within
the
nuclear
envelope
that
mediate
nucleocytoplasmic
exchange.
NPC
diameter
is
thought
to
be
regulated
by
tension,
but
how
such
changes
are
physiologically
linked
cell
differentiation,
where
mechanical
properties
of
nuclei
remodeled
and
mechanosensing
occurs,
remains
unstudied.
Here
we
used
cryo-electron
tomography
show
NPCs
dilate
during
differentiation
mouse
embryonic
stem
cells
into
neural
progenitors.
In
Nup133-deficient
cells,
which
known
display
impaired
however
fail
dilate.
By
analyzing
architectures
individual
with
template
matching,
revealed
structurally
heterogeneous
frequently
disintegrate,
resulting
in
formation
large
openings.
We
propose
elasticity
scaffold
mechanically
safeguards
envelope.
Our
studies
provide
a
molecular
explanation
for
genetic
perturbation
scaffolding
components
macromolecular
causes
tissue-specific
phenotypes.
iScience,
Journal Year:
2024,
Volume and Issue:
27(2), P. 108855 - 108855
Published: Jan. 11, 2024
The
subnuclear
distribution
of
centromeres
is
cooperatively
regulated
by
condensin
II
and
the
linker
nucleoskeleton
cytoskeleton
(LINC)
complex.
However,
other
nuclear
membrane
structures
proteins
are
probably
involved
in
centromere
dynamics
distribution.
Here,
we
focused
on
pore
complex
(NPC),
which
known
to
regulate
gene
expression,
transcription
memory,
chromatin
structure
addition
transport
between
cytoplasm
nucleoplasm.
We
report
here
that
some
nucleoporins
(Nups),
including
Nup85,
Nup133,
CG1,
Nup93b,
NUA,
scattering
Biochemical Society Transactions,
Journal Year:
2025,
Volume and Issue:
53(01)
Published: Feb. 7, 2025
The
nuclear
pore
complex
(NPC)
is
a
vital
regulator
of
molecular
transport
between
the
nucleus
and
cytoplasm
in
eukaryotic
cells.
At
heart
NPC’s
function
are
intrinsically
disordered
phenylalanineglycine-rich
nucleoporins
(FG-Nups),
which
form
dynamic
permeability
barrier
within
central
channel.
This
nature
facilitates
efficient
nucleocytoplasmic
but
also
poses
significant
challenges
to
its
characterization,
especially
nano-confined
environment
NPC.
Recent
advances
experimental
techniques,
such
as
cryo-electron
microscopy,
atomic
force
fluorescence
magnetic
resonance,
along
with
computational
modeling,
have
illuminated
conformational
flexibility
FG-Nups,
underpins
their
functional
versatility.
review
synthesizes
these
advancements,
emphasizing
how
disruptions
FG-Nup
behavior—caused
by
mutations
or
pathological
interactions—contribute
diseases
neurodegenerative
disorders,
aging-related
decline,
viral
infections.
Despite
progress,
persist
deciphering
dynamics
crowded
cellular
environment,
under
conditions.
Addressing
gaps
critical
for
advancing
therapeutic
strategies
targeting
NPC
dysfunction
disease
progression.
Proceedings of the National Academy of Sciences,
Journal Year:
2025,
Volume and Issue:
122(11)
Published: March 14, 2025
Dynamic
processes
involving
biomolecules
are
essential
for
the
function
of
cell.
Here,
we
introduce
an
integrative
method
computing
models
these
based
on
multiple
heterogeneous
sources
information,
including
time-resolved
experimental
data
and
physical
dynamic
processes.
First,
each
time
point,
a
set
coarse
compositional
structural
heterogeneity
is
computed
(heterogeneity
models).
Second,
model,
static
structure
(a
snapshot
model).
Finally,
selected
connected
into
series
trajectories
that
optimize
likelihood
both
transitions
between
them
trajectory
The
demonstrated
by
application
to
assembly
process
human
nuclear
pore
complex
in
context
reforming
envelope
during
mitotic
cell
division,
live-cell
correlated
electron
tomography,
bulk
fluorescence
correlation
spectroscopy–calibrated
quantitative
live
imaging,
model
fully
assembled
complex.
Modeling
improves
precision
over
modeling
alone.
applicable
wide
range
time-dependent
systems
biology
available
broader
scientific
community
through
implementation
open
source
Integrative
Platform
(IMP)
software.