bioRxiv (Cold Spring Harbor Laboratory),
Год журнала:
2022,
Номер
unknown
Опубликована: Дек. 22, 2022
ABSTRACT
It
is
now
established
that
many
viruses
threaten
public
health
establish
condensates
via
phase
transitions
to
complete
their
lifecycles,
and
knowledge
on
such
processes
may
offer
new
strategies
for
antiviral
therapy.
In
the
case
of
influenza
A
virus
(IAV),
liquid
known
as
viral
inclusions,
concentrate
8
distinct
ribonucleoproteins
(vRNPs)
form
IAV
genome
are
viewed
sites
dedicated
assembly
8-partite
genomic
complex.
Despite
not
being
delimited
by
host
membranes,
inclusions
accumulate
membranes
inside
a
result
vRNP
binding
recycling
endocytic
marker
Rab11a,
driver
biogenesis
these
structures.
We
lack
molecular
understanding
how
Rab11a-recycling
endosomes
condensate
specifically
near
endoplasmic
reticulum
(ER)
exit
upon
infection.
show
here
interact
with
ER
fuse,
divide
slide.
uncover
that,
contrary
previous
indications,
reported
reduction
in
activity
regulated
process
rather
than
competition
cellular
resources
involving
novel
role
factor
ATG9A.
infection,
ATG9A
mediates
removal
carrying
vRNPs
from
microtubules.
observe
usage
microtubules
rescued
when
depleted,
which
prevents
condensation
Rab11a
ER.
The
failure
produce
accumulates
cytosol,
reduces
release
infectious
virions.
propose
supports
dynamics
facilitating
formation.
This
work
advances
our
epidemic
pandemic
genomes
formed.
also
reveals
plasticity
pathway
undergo
response
disclosing
roles
beyond
its
classical
involvement
autophagy.
bioRxiv (Cold Spring Harbor Laboratory),
Год журнала:
2025,
Номер
unknown
Опубликована: Янв. 29, 2025
Summary
Establishment
of
N.
benthamiana
as
a
robust
biofactory
is
complicated
by
issues
such
product
toxicity
and
proteolytic
degradation
target
proteins
/
introduced
enzymes.
Here
we
investigate
whether
biomolecular
condensates
can
be
used
to
address
these
problems.
We
engineered
in
leaves
using
transient
expression
synthetic
modular
scaffolds.
The
vivo
properties
the
that
resulted
were
consistent
with
them
being
liquid-like
bodies
thermodynamic
features
typical
multicomponent
phase-separating
systems.
show
recruitment
enzymes
led
several
fold
yield
increases
one-
three-step
metabolic
pathways
(citramalate
biosynthesis
poly-3-hydroxybutyrate
(PHB)
biosynthesis,
respectively).
This
enhanced
could
for
reasons
including
improved
enzyme
kinetics,
metabolite
channelling
or
avoidance
cytotoxicity
retention
pathway
within
condensate,
which
was
demonstrated
PHB.
However,
also
observed
several-fold
increase
amount
accumulated
when
they
targeted
condensates.
suggests
more
stable
localised
condensate
than
freely
diffusing
cytosol.
hypothesise
this
stability
likely
main
driver
increased
production.
Our
findings
provide
foundation
leveraging
plant
engineering
advance
versatile
industrial
applications.
Plant Biotechnology Journal,
Год журнала:
2025,
Номер
unknown
Опубликована: Апрель 9, 2025
Summary
The
establishment
of
Nicotiana
benthamiana
as
a
robust
biofactory
is
complicated
by
issues
such
product
toxicity
and
proteolytic
degradation
target
proteins/introduced
enzymes.
Here
we
investigate
whether
biomolecular
condensates
can
be
used
to
address
these
problems.
We
engineered
in
N.
leaves
using
transient
expression
synthetic
modular
scaffolds.
vivo
properties
the
that
resulted
were
consistent
with
them
being
liquid‐like
bodies
thermodynamic
features
typical
multicomponent
phase‐separating
systems.
show
recruitment
enzymes
led
several‐fold
yield
increases
one‐
three‐step
metabolic
pathways
(citramalate
biosynthesis
poly‐3‐hydroxybutyrate
(PHB)
biosynthesis,
respectively).
This
enhanced
could
for
several
reasons
including
improved
enzyme
kinetics,
metabolite
channelling
or
avoidance
cytotoxicity
retention
pathway
within
condensate,
which
was
demonstrated
PHB.
However,
also
observed
increase
amount
accumulated
when
they
targeted
condensates.
suggests
more
stable
localised
condensate
than
freely
diffusing
cytosol.
hypothesise
this
stability
likely
main
driver
increased
production.
Our
findings
provide
foundation
leveraging
plant
engineering
advance
versatile
industrial
applications.
Nature Communications,
Год журнала:
2025,
Номер
16(1)
Опубликована: Апрель 30, 2025
O-GlcNAcylation
plays
critical
roles
in
the
regulation
of
protein
functions
and
cellular
activities,
including
interactions
with
other
macromolecules.
While
formation
biomolecular
condensates
(or
biocondensates)
regulated
by
a
few
individual
proteins
has
been
reported,
systematic
investigation
on
biocondensate
remains
to
be
explored.
Here
we
systematically
study
regulating
solubility
its
impacts
RNA-protein
using
mass
spectrometry-based
chemoproteomics.
Unexpectedly,
observe
system-wide
decrease
modified
O-GlcNAcylation,
glycoproteins
involved
focal
adhesion
actin
binding
exhibiting
most
significant
decrease.
Furthermore,
sites
located
disordered
regions
fewer
acidic
aromatic
residues
nearby
are
related
greater
drop
solubility.
Additionally,
discover
that
specific
group
events
promotes
dissociation
under
heat
stress,
while
some
enhance
during
recovery
phase.
Using
site
mutagenesis,
inhibition
O-GlcNAc
transferase,
fluorescence
microscopy,
validate
regulates
biocondensates
for
YTHDF3
NUFIP2.
This
work
advances
our
understanding
condensates.
Zoonotic
viruses
rank
among
the
greatest
threats
to
public
health,
with
urbanization
and
global
warming
accelerating
their
emergence
spread.
As
risk
of
future
pandemics
grows,
innovative
tools
are
needed
deepen
our
understanding
viral
pathogenesis
enhance
pandemic
preparedness.
Nonviral
protein
cages
provide
a
versatile
platform
for
studying
mechanisms,
virus-host
interactions,
designing
next-generation
therapeutic
approaches,
making
them
powerful
assets
in
fight
against
threats.
iScience,
Год журнала:
2024,
Номер
27(3), С. 109100 - 109100
Опубликована: Фев. 2, 2024
Influenza
A
virus
(IAV)
employs
multiple
strategies
to
manipulate
cellular
mechanisms
and
support
proper
virion
formation
propagation.
In
this
study,
we
performed
a
detailed
analysis
of
the
interplay
between
IAV
host
cells'
proteostasis
throughout
entire
infectious
cycle.
We
reveal
that
infection
activates
inositol
requiring
enzyme
1
(IRE1)
branch
unfolded
protein
response,
activation
is
important
for
an
efficient
infection.
further
observed
accumulation
virus-induced
insoluble
aggregates,
containing
both
viral
proteins,
associated
with
dysregulation
cell
RNA
metabolism.
Our
data
indicate
propagation
favors
final
steps
cycle,
more
specifically
assembly.
These
findings
additional
by
which
disrupts
uncovers
new
targets
can
be
explored
development
host-directed
antiviral
strategies.
International Journal of Molecular Sciences,
Год журнала:
2024,
Номер
25(13), С. 6981 - 6981
Опубликована: Июнь 26, 2024
In
the
field
of
virology,
liquid-liquid
phase
separation
(LLPS)
has
emerged
as
a
pivotal
mechanism
enabling
compartmentalization
required
for
specific
steps
viral
replication
cycle
[...].
bioRxiv (Cold Spring Harbor Laboratory),
Год журнала:
2023,
Номер
unknown
Опубликована: Сен. 11, 2023
Abstract
Influenza
A
virus
(IAV)
is
one
of
the
main
causes
annual
respiratory
epidemics
in
humans.
IAV
employs
multiple
strategies
to
evade
host
immunity
and
hijack
cellular
mechanisms
support
proper
virion
formation
propagation.
Some
these
encompass
manipulation
pathways
involved
protein
homeostasis,
leading
changes
proteome
distribution
within
cell.
In
this
study,
we
performed
a
detailed
analysis
interplay
between
cells’
proteostasis
throughout
entire
infectious
cycle.
We
reveal
that
infection
induces
activation
inositol
requiring
enzyme
1
(IRE1)
branch
unfolded
response
(UPR),
at
an
stage
coincides
with
high
rates
viral
translation.
This
particularly
important
for
infection,
as
attenuation
production
was
observed
upon
IRE1
inhibition.
Concomitantly
UPR
activation,
accumulation
virus-induced
insoluble
aggregates,
which
contain
both
proteins
are
associated
dysregulation
cell
RNA
metabolism.
demonstrate
propagation,
its
prevention
using
quinoline-steroid
hybrid
compound
significantly
reduces
number
produced
particles.
Our
data
suggests
aggregates
favors
final
steps
cycle,
more
specifically
assembly.
findings
additional
by
disrupts
favor
uncover
new
targets
can
be
explored
development
host-directed
antiviral
strategies.