bioRxiv (Cold Spring Harbor Laboratory),
Год журнала:
2024,
Номер
unknown
Опубликована: Ноя. 22, 2024
ABSTRACT
DDX3X
is
an
X-linked
RNA
helicases
that
escapes
X
chromosome
inactivation
and
expressed
at
higher
levels
in
female
brains.
Mutations
are
associated
with
intellectual
disability
(ID)
autism
spectrum
disorder
(ASD)
predominantly
identified
females.
Using
cellular
mouse
models,
we
show
Ddx3x
mediates
sexual
dimorphisms
brain
development
a
molecular,
cellular,
behavioral
level.
During
cortical
neuronal
development,
sustains
female-biased
signature
of
enhanced
ribosomal
biogenesis
mRNA
translation.
Female
neurons
display
proteins
larger
nucleoli,
these
sex
obliterated
by
loss.
regulates
dendritic
outgrowth
sex-
dose-dependent
manner
both
male
neurons,
spine
only
neurons.
Further,
ablating
conditionally
forebrain
sufficient
to
yield
sex-specific
changes
developmental
outcomes
motor
function.
Together,
findings
pose
as
mediator
differentiation
during
neurodevelopment
open
new
avenues
understand
differences
health
disease.
Annual Review of Biochemistry,
Год журнала:
2024,
Номер
93(1), С. 79 - 108
Опубликована: Апрель 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.
Trends in Molecular Medicine,
Год журнала:
2023,
Номер
29(9), С. 726 - 739
Опубликована: Июль 6, 2023
RNA
molecules
rely
on
proteins
across
their
life
cycle.
DDX3X
encodes
an
X-linked
DEAD-box
helicase
with
a
Y-linked
paralog,
DDX3Y.
is
central
to
the
cycle
and
implicated
in
many
conditions,
including
cancer
neurodevelopmental
disorder
syndrome.
DDX3X-linked
conditions
often
exhibit
sex
differences,
possibly
due
differences
between
expression
or
function
of
X-
paralogs
DDX3X-related
diseases
have
different
mutational
landscapes,
indicating
roles
DDX3X.
Understanding
role
normal
disease
states
will
inform
understanding
disease.
We
review
DDX3Y,
discuss
how
mutation
type
bias
contribute
human
involving
DDX3X,
possible
DDX3X-targeting
treatments.
Abstract
Biomolecular
condensates
are
cellular
structures
composed
of
membraneless
assemblies
comprising
proteins
or
nucleic
acids.
The
formation
these
requires
components
to
change
from
a
state
solubility
separation
the
surrounding
environment
by
undergoing
phase
transition
and
condensation.
Over
past
decade,
it
has
become
widely
appreciated
that
biomolecular
ubiquitous
in
eukaryotic
cells
play
vital
role
physiological
pathological
processes.
These
may
provide
promising
targets
for
clinic
research.
Recently,
series
processes
have
been
found
associated
with
dysfunction
condensates,
range
methods
demonstrated
modulate
condensates.
A
more
extensive
description
is
urgently
needed
development
novel
therapies.
In
this
review,
we
summarized
current
understanding
molecular
mechanisms
their
formation.
Moreover,
reviewed
functions
therapeutic
diseases.
We
further
highlighted
available
regulatory
methods,
discussed
significance
challenges
targeting
Reviewing
latest
developments
condensate
research
could
be
essential
translating
our
knowledge
on
use
clinical
strategies.
Molecular Cell,
Год журнала:
2023,
Номер
83(22), С. 4174 - 4189.e7
Опубликована: Ноя. 1, 2023
Alphaviruses
are
a
large
group
of
re-emerging
arthropod-borne
RNA
viruses.
The
compact
viral
genomes
harbor
diverse
structures
that
facilitate
replication.
These
can
be
recognized
by
antiviral
cellular
RNA-binding
proteins,
including
DExD-box
(DDX)
helicases,
bind
RNAs
to
control
infection.
full
spectrum
DDXs
and
the
remain
unclear.
Genetic
screening
identified
DDX39A
as
against
alphavirus
chikungunya
virus
(CHIKV)
other
medically
relevant
alphaviruses.
Upon
infection,
predominantly
nuclear
accumulates
in
cytoplasm
inhibiting
replication,
independent
canonical
interferon
pathway.
Biochemically,
binds
CHIKV
genomic
RNA,
interacting
with
5′
conserved
sequence
element
(5′CSE),
which
is
essential
for
activity
DDX39A.
Altogether,
relocalization
binding
structural
attenuates
revealing
previously
unknown
layer
Cell Reports,
Год журнала:
2024,
Номер
43(6), С. 114248 - 114248
Опубликована: Май 24, 2024
Cyclic
GMP-AMP
synthase
(cGAS)
undergoes
liquid-liquid
phase
separation
(LLPS)
to
trigger
downstream
signaling
upon
double-stranded
DNA
(dsDNA)
stimulation,
and
the
condensed
cGAS
colocalizes
with
stress
granules
(SGs).
However,
molecular
mechanism
underlying
modulation
of
activation
by
SGs
remains
elusive.
In
this
study,
we
show
that
USP8
is
localized
dsDNA
stimulation
potentiates
cGAS-stimulator
interferon
genes
(STING)
signaling.
A
inhibitor
ameliorates
pathological
inflammation
in
Trex1−/−
mice.
Systemic
lupus
erythematosus
(SLE)
databases
indicate
a
positive
correlation
between
expression
SLE.
Mechanistic
study
shows
SG
protein
DDX3X
promotes
manner
dependent
on
its
intrinsic
LLPS.
cleaves
K27-linked
ubiquitin
chains
from
intrinsically
disordered
region
(IDR)
enhance
condensation.
conclusion,
demonstrate
catalyzes
deubiquitination
facilitate
condensation
inhibiting
promising
strategy
for
alleviating
cGAS-mediated
autoimmune
diseases.
Cell Communication and Signaling,
Год журнала:
2024,
Номер
22(1)
Опубликована: Фев. 21, 2024
Abstract
Phase
separation
is
a
cellular
phenomenon
where
macromolecules
aggregate
or
segregate,
giving
rise
to
biomolecular
condensates
resembling
"droplets"
and
forming
distinct,
membrane-free
compartments.
This
process
pervasive
in
biological
cells,
contributing
various
essential
functions.
However,
when
phase
goes
awry,
leading
abnormal
molecular
aggregation,
it
can
become
driving
factor
the
development
of
diseases,
including
tumor.
Recent
investigations
have
unveiled
intricate
connection
between
dysregulated
tumor
pathogenesis,
highlighting
its
potential
as
novel
therapeutic
target.
article
provides
an
overview
recent
research,
with
particular
emphasis
on
role
tumor,
implications,
outlines
avenues
for
further
exploration
this
intriguing
field.
Journal of Virology,
Год журнала:
2024,
Номер
unknown
Опубликована: Авг. 30, 2024
RNA
helicases
are
integral
in
metabolism,
performing
important
roles
cellular
homeostasis
and
stress
responses.
In
particular,
the
DExD/H-box
(DDX)
helicase
family
possesses
a
conserved
catalytic
core
that
binds
structural
features
rather
than
specific
sequences
targets.
DDXs
have
critical
all
aspects
of
metabolism
including
ribosome
biogenesis,
translation,
export,
stability.
Importantly,
functional
specialization
within
this
arises
from
divergent
N
C
termini
is
driven
at
least
part
by
gene
duplications
with
18
42
human
having
paralogs.
addition
to
their
key
homeostatic
control
RNA,
these
factors
virus
infection.
The
canonical
RIG-I-like
receptors
(RLRs)
play
pivotal
cytoplasmic
sensing
viral
structures,
inducing
antiviral
expression.
Additional
function
as
sensors
or
regulators,
further
diversifying
innate
immune
defense
arsenal.
Moreover,
some
been
coopted
viruses
facilitate
replication.
Altogether,
DDX
exhibit
specificity,
playing
intricate
host
defense.
This
review
will
discuss
mechanisms
which
recognize
diverse
structures
RNAs,
how
impacts
processing
