Journal of Neurochemistry,
Journal Year:
2024,
Volume and Issue:
unknown
Published: July 8, 2024
Abstract
DDX3X
syndrome
is
a
neurodevelopmental
disorder
accounting
for
up
to
3%
of
cases
intellectual
disability
(ID)
and
affecting
primarily
females.
Individuals
diagnosed
with
can
also
present
behavioral
challenges,
motor
delays
movement
disorders,
epilepsy,
congenital
malformations.
caused
by
mutations
in
the
X‐linked
gene
,
which
encodes
DEAD‐box
RNA
helicase
critical
roles
metabolism,
including
mRNA
translation.
Emerging
discoveries
from
animal
models
are
unveiling
fundamental
role
neuronal
differentiation
development,
especially
neocortex.
Here,
we
review
current
knowledge
genetic
neurobiological
mechanisms
underlying
their
relationship
clinical
phenotypes.
image
Science,
Journal Year:
2024,
Volume and Issue:
384(6698)
Published: May 23, 2024
RNA
splicing
is
highly
prevalent
in
the
brain
and
has
strong
links
to
neuropsychiatric
disorders;
yet,
role
of
cell
type-specific
transcript-isoform
diversity
during
human
development
not
been
systematically
investigated.
In
this
work,
we
leveraged
single-molecule
long-read
sequencing
deeply
profile
full-length
transcriptome
germinal
zone
cortical
plate
regions
developing
neocortex
at
tissue
single-cell
resolution.
We
identified
214,516
distinct
isoforms,
which
72.6%
were
novel
(not
previously
annotated
Gencode
version
33),
uncovered
a
substantial
contribution
diversity-regulated
by
binding
proteins-in
defining
cellular
identity
neocortex.
comprehensive
isoform-centric
gene
annotation
reprioritize
thousands
rare
de
novo
risk
variants
elucidate
genetic
mechanisms
for
disorders.
Mutations
in
the
RNA
helicase,
DDX3X
,
are
a
leading
cause
of
Intellectual
Disability
and
present
as
syndrome,
neurodevelopmental
disorder
associated
with
cortical
malformations
autism.
Yet,
cellular
molecular
mechanisms
by
which
controls
development
largely
unknown.
Here,
using
mouse
model
Ddx3x
loss-of-function
we
demonstrate
that
directs
translational
cell
cycle
control
neural
progenitors,
underlies
precise
corticogenesis.
First,
show
brain
is
sensitive
to
dosage;
complete
loss
from
progenitors
causes
microcephaly
females,
whereas
hemizygous
males
heterozygous
females
reduced
neurogenesis
without
marked
microcephaly.
In
addition,
sexually
dimorphic,
its
paralog,
Ddx3y
compensates
for
developing
male
neocortex.
Using
live
imaging
promotes
neuronal
generation
regulating
both
duration
neurogenic
divisions.
Finally,
use
ribosome
profiling
vivo
discover
repertoire
translated
transcripts
including
those
DDX3X-dependent
essential
neurogenesis.
Our
study
reveals
invaluable
new
insights
into
etiology
implicating
dysregulated
progenitor
dynamics
translation
pathogenic
mechanisms.
Cancers,
Journal Year:
2024,
Volume and Issue:
16(6), P. 1131 - 1131
Published: March 12, 2024
The
DEAD
(Asp-Glu-Ala-Asp)-box
helicase
3
X-linked
(DDX3X)
protein
participates
in
many
aspects
of
mRNA
metabolism
and
stress
granule
(SG)
formation.
DDX3X
has
also
been
associated
with
signal
transduction
cell
cycle
regulation
that
are
important
maintaining
cellular
homeostasis.
Malfunctions
have
implicated
multiple
cancers,
including
brain
cancer,
leukemia,
prostate
head
neck
cancer.
Recently,
literature
reported
SG-associated
cancer
drug
resistance,
which
correlates
a
negative
disease
prognosis.
Based
on
the
connections
between
DDX3X,
SG
formation,
pathology,
targeting
may
be
promising
direction
for
therapeutics
development.
In
this
review,
we
describe
biological
functions
terms
metabolism,
transduction,
regulation.
Furthermore,
summarize
contributions
formation
adaptation.
Finally,
discuss
relationships
SG,
current
research
progress
several
inhibitors
treatment.
Frontiers in Cell and Developmental Biology,
Journal Year:
2022,
Volume and Issue:
10
Published: Oct. 25, 2022
The
human
DEAD-box
protein
DDX3X
is
an
RNA
remodelling
enzyme
that
has
been
implicated
in
various
aspects
of
metabolism.
In
addition,
like
many
proteins,
it
non-conventional
functions
are
independent
its
enzymatic
activity,
e.g.,
acts
as
adaptor
molecule
innate
immune
signalling
pathways.
linked
to
several
diseases.
For
example,
somatic
mutations
were
identified
cancers,
and
de
novo
germline
cause
a
neurodevelopmental
condition
now
termed
‘DDX3X
syndrome’.
also
important
host
factor
different
viral
infections,
where
can
have
pro-or
anti-viral
effects
depending
on
the
specific
virus.
regulation
translation
initiation
for
mRNA
transcripts
likely
central
cellular
function
DDX3X,
yet
questions
regarding
exact
targets
mechanisms
action
remain
unanswered.
this
review,
we
explore
current
knowledge
about
DDX3X’s
physiological
summarise
interactions
with
machinery.
A
role
translational
reprogramming
during
stress
emerging,
may
be
involved
granule
formation
mediating
non-canonical
initiation.
Finally,
discuss
DDX3X-mediated
infections.
Dysregulation
contributes
involvement
disease
pathophysiology.
Thus,
better
understanding
regulating
important,
so
potentially
develop
therapeutic
strategies
overcoming
negative
dysregulation.
Trends in Molecular Medicine,
Journal Year:
2023,
Volume and Issue:
29(9), P. 726 - 739
Published: July 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.
