Science Translational Medicine,
Journal Year:
2024,
Volume and Issue:
16(767)
Published: Oct. 2, 2024
The
mechanisms
underlying
stimuli-induced
dynamic
structural
remodeling
of
RNAs
for
the
maintenance
cellular
physiological
function
and
survival
remain
unclear.
Here,
we
showed
that
in
MGMT
promoter–methylated
glioblastoma
(GBM),
RNA
helicase
DEAD-box
46
(DDX46)
is
phosphorylated
by
temozolomide
(TMZ)–activated
checkpoint
kinase
1
(CHK1),
resulting
a
dense-to-loose
conformational
change
an
increase
DDX46
activity.
DDX46-mediated
tertiary
LINC01956
exposes
binding
motifs
to
3′
untranslated
region
O
6
-methylguanine
DNA
methyltransferase
(
).
This
accelerates
recruitment
mRNA
export
machinery
transportation
from
nucleus
cytoplasm,
leading
increased
abundance
TMZ
resistance.
Using
patient-derived
xenograft
(PDX)
tumor
organoid
models,
found
treatment
with
CHK1
inhibitor
SRA737abolishes
TMZ-induced
subsequent
up-regulation,
resensitizing
TMZ-resistant
GBM
TMZ.
In
conclusion,
these
findings
highlight
mechanism
temozolomide-induced
may
represent
potential
therapeutic
strategy
patients
GBM.
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.
The Journal of Cell Biology,
Journal Year:
2024,
Volume and Issue:
223(6)
Published: March 27, 2024
Stress
granules
and
P-bodies
are
ribonucleoprotein
(RNP)
that
accumulate
during
the
stress
response
due
to
condensation
of
untranslating
mRNPs.
form
in
part
by
intermolecular
RNA–RNA
interactions
can
be
limited
components
RNA
chaperone
network,
which
inhibits
RNA-driven
aggregation.
Herein,
we
demonstrate
DEAD-box
helicase
DDX6,
a
P-body
component,
also
limit
formation
granules,
independent
P-bodies.
In
an
ATPase,
RNA-binding
dependent
manner,
DDX6
limits
partitioning
itself
other
RNPs
into
granules.
When
limited,
proteins
normally
partition
between
show
increased
accumulation
within
Moreover,
loss
4E-T,
DCP1A
increases
docking
with
depends
on
CNOT1
PAT1B.
Taken
together,
these
observations
identify
new
role
for
limiting
influence
granule
composition
Journal of Experimental Botany,
Journal Year:
2022,
Volume and Issue:
74(7), P. 2295 - 2310
Published: Nov. 23, 2022
RNA
helicases
(RHs)
are
a
family
of
ubiquitous
enzymes
that
alter
structures
and
remodel
ribonucleoprotein
complexes
typically
using
energy
from
the
hydrolysis
ATP.
RHs
involved
in
various
aspects
processing
metabolism,
exemplified
by
transcriptional
regulation,
pre-mRNA
splicing,
miRNA
biogenesis,
liquid-liquid
phase
separation,
rRNA
among
other
molecular
processes.
Through
these
mechanisms,
contribute
to
vegetative
reproductive
growth,
as
well
abiotic
biotic
stress
responses
throughout
life
cycle
plants.
In
this
review,
we
systematically
characterize
RH-featured
domains
signature
motifs
Arabidopsis.
We
also
summarize
functions
mechanisms
biological
processes
plants
with
focus
on
DEAD-box
DEAH-box
helicases,
aiming
present
latest
understanding
plant
biology.
Chemical Reviews,
Journal Year:
2023,
Volume and Issue:
123(14), P. 9065 - 9093
Published: April 28, 2023
Biomolecular
condensates
are
reversible
compartments
that
form
through
a
process
called
phase
separation.
Post-translational
modifications
like
ADP-ribosylation
can
nucleate
the
formation
of
these
by
accelerating
self-association
proteins.
Poly(ADP-ribose)
(PAR)
chains
remarkably
transient
with
turnover
rates
on
order
minutes,
yet
they
be
required
for
granules
in
response
to
oxidative
stress,
DNA
damage,
and
other
stimuli.
Moreover,
accumulation
PAR
is
linked
adverse
transitions
neurodegenerative
diseases,
including
Alzheimer's
disease,
Parkinson's
amyotrophic
lateral
sclerosis.
In
this
review,
we
provide
primer
how
synthesized
regulated,
diverse
structures
chemistries
modifications,
protein–PAR
interactions.
We
review
substantial
progress
recent
efforts
determine
molecular
mechanism
PAR-mediated
separation,
further
delineate
inhibitors
polymerases
may
effective
treatments
pathologies.
Finally,
highlight
need
rigorous
biochemical
interrogation
vivo
vitro
clarify
exact
pathway
from
PARylation
condensate
formation.
Journal of the American Chemical Society,
Journal Year:
2023,
Volume and Issue:
145(17), P. 9571 - 9583
Published: April 16, 2023
A
hallmark
of
Huntington's
disease
(HD)
is
a
prolonged
polyglutamine
sequence
in
the
huntingtin
protein
and,
correspondingly,
an
expanded
cytosine,
adenine,
and
guanine
(CAG)
triplet
repeat
region
mRNA.
majority
studies
investigating
pathology
were
concerned
with
toxic
protein,
but
mRNA
moved
into
focus
due
to
its
recruitment
RNA
foci
emerging
novel
therapeutic
approaches
targeting
CAG-RNA
that
it
forms
stable
hairpin
vitro
which
seems
be
crucial
for
specific
interactions.
Using
in-cell
folding
experiments,
we
show
largely
destabilized
cells
compared
dilute
buffer
solutions
remains
folded
cytoplasm
nucleus.
Surprisingly,
found
same
stability
nucleoplasm
nuclear
speckles
under
physiological
conditions
suggesting
does
not
undergo
conformational
transition
upon
speckles.
We
metabolite
adenosine
triphosphate
(ATP)
plays
role
promoting
unfolding,
enabling
preserving
mobility.
experiments
molecular
dynamics
simulations,
ATP
effects
can
attributed
direct
interaction
nucleobases
rather
than
acting
as
"a
fuel"
helicase
activity.
ATP-driven
changes
homeostasis
could
disease-relevant
since
mitochondrial
function
affected
HD
progression
leading
decline
cellular
levels.
