Annual Review of Biochemistry,
Journal Year:
2024,
Volume and Issue:
93(1), P. 79 - 108
Published: April 10, 2024
DEAD-
and
DExH-box
ATPases
(DDX/DHXs)
are
abundant
highly
conserved
cellular
enzymes
ubiquitously
involved
in
RNA
processing.
By
remodeling
RNA–RNA
RNA–protein
interactions,
they
often
function
as
gatekeepers
that
control
the
progression
of
diverse
maturation
steps.
Intriguingly,
most
DDX/DHXs
localize
to
membraneless
organelles
(MLOs)
such
nucleoli,
nuclear
speckles,
stress
granules,
or
processing
bodies.
Recent
findings
suggest
not
only
localization
MLOs
can
promote
interaction
between
their
targets
but
also
key
regulators
MLO
formation
turnover
through
condensation
ATPase
activity.In
this
review,
we
describe
molecular
ribosome
biogenesis,
messenger
splicing,
export,
translation,
storage
decay
well
association
with
prominent
MLOs.
We
discuss
how
enzymatic
is
linked
DDX/DHX
condensation,
accumulation
ribonucleoprotein
particles
dynamics.
Future
research
will
reveal
these
processes
orchestrate
life
cycle
space
time.
Nucleic Acids Research,
Journal Year:
2022,
Volume and Issue:
50(15), P. 8599 - 8614
Published: Aug. 5, 2022
Abstract
SRRM2
is
a
nuclear-speckle
marker
containing
multiple
disordered
domains,
whose
dysfunction
associated
with
several
human
diseases.
Using
mainly
EGFP-SRRM2
knock-in
HEK293T
cells,
we
show
that
forms
biomolecular
condensates
satisfying
most
hallmarks
of
liquid-liquid
phase
separation,
including
spherical
shape,
dynamic
rearrangement,
coalescence
and
concentration
dependence
supported
by
in
vitro
experiments.
Live-cell
imaging
shows
organizes
nuclear
speckles
along
the
cell
cycle.
As
bona-fide
splicing
factor
present
spliceosome
structures,
deficiency
induces
skipping
cassette
exons
short
introns
weak
splice
sites,
tending
to
change
large
protein
domains.
In
THP-1
myeloid-like
depletion
compromises
viability,
upregulates
differentiation
markers,
sensitizes
cells
anti-leukemia
drugs.
FES
isoform
attenuates
innate
inflammatory
responses,
MUC1
isoforms
undergo
shedding
oncogenic
properties.
We
conclude
acts
as
scaffold
organize
speckles,
regulating
alternative
immunity
homeostasis.
Cell,
Journal Year:
2024,
Volume and Issue:
187(2), P. 331 - 344.e17
Published: Jan. 1, 2024
Enhancers
are
distal
DNA
elements
believed
to
loop
and
contact
promoters
control
gene
expression.
Recently,
we
found
diffraction-sized
transcriptional
condensates
at
genes
controlled
by
clusters
of
enhancers
(super-enhancers).
However,
a
direct
function
endogenous
in
controlling
expression
remains
elusive.
Here,
develop
live-cell
super-resolution
multi-color
3D-imaging
approaches
investigate
putative
roles
the
regulation
super-enhancer
Sox2.
In
contrast
enhancer
distance,
find
instead
that
condensate's
positional
dynamics
better
predictor
A
basal
bursting
occurs
when
condensate
is
far
(>1
μm),
but
burst
size
frequency
enhanced
moves
proximity
(<1
μm).
Perturbations
cohesin
local
do
not
prevent
affect
its
enhancement.
We
propose
three-way
kissing
model
whereby
interacts
transiently
with
locus
regulatory
bursting.
Nature Physics,
Journal Year:
2023,
Volume and Issue:
19(4), P. 586 - 596
Published: Feb. 2, 2023
Phase
separation
of
biomolecules
into
condensates
has
emerged
as
a
mechanism
for
intracellular
organization
and
affects
many
processes,
including
reaction
pathways
through
the
clustering
enzymes
pathway
intermediates.
Precise
rapid
spatiotemporal
control
reactions
by
requires
tuning
their
sizes.
However,
physical
processes
that
govern
distribution
condensate
sizes
remain
unclear.
Here
we
show
both
native
synthetic
display
an
exponential
size
distribution,
which
is
captured
Monte
Carlo
simulations
fast
nucleation
followed
coalescence.
In
contrast,
pathological
aggregates
exhibit
power-law
distribution.
These
distinct
behaviours
reflect
relative
importance
coalescence
kinetics.
We
demonstrate
this
utilizing
combination
to
probe
underlying
mechanisms
determining
size.
The
appearance
distributions
abrupt
versus
under
continuous
may
general
principle
determines
distributions.
Nature Chemistry,
Journal Year:
2024,
Volume and Issue:
16(7), P. 1073 - 1082
Published: Feb. 21, 2024
Endogenous
biomolecular
condensates,
composed
of
a
multitude
proteins
and
RNAs,
can
organize
into
multiphasic
structures
with
compositionally
distinct
phases.
This
organization
is
generally
understood
to
be
critical
for
facilitating
their
proper
biological
function.
However,
the
biophysical
principles
driving
multiphase
formation
are
not
completely
understood.
Here
we
use
in
vivo
condensate
reconstitution
experiments
coarse-grained
molecular
simulations
investigate
how
oligomerization
sequence
interactions
modulate
condensates.
We
demonstrate
that
increasing
state
an
intrinsically
disordered
protein
results
enhanced
immiscibility
formation.
Interestingly,
find
tunes
miscibility
asymmetric
manner,
effect
being
more
pronounced
when
protein,
exhibiting
stronger
homotypic
interactions,
oligomerized.
Our
findings
suggest
flexible
mechanism
cells
exploit
tune
internal
condensates
associated
functions.
