Dynamic interactions of retroviral Gag condensates with nascent viral RNA at transcriptional burst sites: implications for genomic RNA packaging
bioRxiv (Cold Spring Harbor Laboratory),
Journal Year:
2025,
Volume and Issue:
unknown
Published: Jan. 12, 2025
Abstract
Retroviruses
are
responsible
for
significant
pathology
in
humans
and
animals,
including
the
acquired
immunodeficiency
syndrome
a
wide
range
of
malignancies.
A
crucial
yet
poorly
understood
step
replication
cycle
is
recognition
selection
unspliced
viral
RNA
(USvRNA)
by
retroviral
Gag
protein,
which
binds
to
psi
(Ψ)
packaging
sequence
5’
leader,
package
it
as
genomic
(gRNA)
into
nascent
virions.
It
was
previously
thought
that
initially
bound
gRNA
cytoplasm.
However,
previous
studies
demonstrated
Rous
sarcoma
virus
(RSV)
protein
traffics
transiently
through
nucleus,
necessary
efficient
packaging.
These
data
formed
strong
premise
hypothesis
selects
at
transcription
sites
location
highest
concentration
USvRNA
molecules
cell.
In
support
this
model,
using
fixed
cells
infected
with
RSV
revealed
co-localizes
large
nuclear
foci
representing
transcriptional
burst
sites.
To
test
idea,
we
used
single
molecule
labeling
imaging
techniques
visualize
fluorescently-tagged,
actively
transcribing
genomes,
proteins
living
cells.
condensates
were
observed
co-localized
sites,
forming
co-
localized
ribonucleoprotein
complexes
(vRNPs).
results
novel
paradigm
assembly
interacts
dynamic
kissing
interaction
capture
incorporation
Language: Английский
How Transcriptional Bursting and mRNA Production Affect Precise Timing of Cell Lysis Phenomena
The Journal of Physical Chemistry B,
Journal Year:
2025,
Volume and Issue:
unknown
Published: April 7, 2025
Bacterial
viruses
infect
bacterial
cells
and
stimulate
the
production
of
holin
proteins
that
accumulate
in
cellular
membranes.
When
number
such
reaches
a
threshold,
membrane
permeabilizes
cell
is
destroyed
process
known
as
lysis.
Experimental
studies
indicate
lysis
occurs
at
specific
times,
although
underlying
molecular
mechanisms
precise
timing
remain
not
well
understood.
Recently,
theoretical
framework
has
been
introduced
to
explain
these
phenomena
coupling
between
stochastic
processes
holins
accumulation
breaking
leads
threshold
behavior.
However,
this
approach
does
account
for
many
biologically
important
In
work,
we
investigated
role
transcriptional
bursting
mRNA
on
dynamics
The
original
extended,
allowing
us
evaluate
under
more
realistic
biological
conditions
using
analytical
calculations
Monte
Carlo
computer
simulations.
It
shown
explicitly
random
transcription
do
affect
threshold-like
lysis,
they
influence
absolute
values
maximal
thresholds
their
distributions.
also
found
effect
generally
stronger
than
due
bursting.
Physical-chemical
arguments
observations
are
presented.
Thus,
our
analysis
suggests
robust
phenomenon
despite
involving
multiple
biochemical
processes.
Our
clarifies
some
mechanistic
aspects
complex
Language: Английский