Life Science Alliance,
Год журнала:
2024,
Номер
7(11), С. e202402764 - e202402764
Опубликована: Авг. 29, 2024
Mitochondrial
gene
expression
is
a
compartmentalised
process
essential
for
metabolic
function.
The
replication
and
transcription
of
mitochondrial
DNA
(mtDNA)
take
place
at
nucleoids,
whereas
the
subsequent
processing
maturation
RNA
(mtRNA)
mitoribosome
assembly
are
localised
to
granules.
bidirectional
circular
mtDNA
can
lead
hybridisation
polycistronic
transcripts
formation
immunogenic
double-stranded
(mt-dsRNA).
However,
mechanisms
that
regulate
mt-dsRNA
localisation
homeostasis
largely
unknown.
With
super-resolution
microscopy,
we
show
overlaps
with
core
associated
proteins
granules
but
not
nucleoids.
Mt-dsRNA
foci
accumulate
upon
stimulation
cell
proliferation
their
abundance
depends
on
ribonucleotide
supply
by
nucleoside
diphosphate
kinase,
NME6.
Consequently,
profuse
in
cultured
cancer
cells
malignant
human
tumour
biopsies.
Our
results
establish
new
link
between
nucleic
acid
homeostasis.
Nucleic Acids Research,
Год журнала:
2023,
Номер
51(22), С. 12443 - 12458
Опубликована: Ноя. 1, 2023
The
dNTPase
activity
of
tetrameric
SAM
and
HD
domain
containing
deoxynucleoside
triphosphate
triphosphohydrolase
1
(SAMHD1)
plays
a
critical
role
in
cellular
dNTP
regulation.
SAMHD1
also
associates
with
stalled
DNA
replication
forks,
repair
foci,
ssRNA
telomeres.
above
functions
require
nucleic
acid
binding
by
SAMHD1,
which
may
be
modulated
its
oligomeric
state.
Here
we
establish
cryo-EM
biochemical
studies
that
the
guanine-specific
A1
activator
site
each
monomer
is
used
to
target
enzyme
guanine
nucleotides
within
single-stranded
(ss)
RNA.
Remarkably,
strands
single
base
induce
dimeric
while
two
or
more
guanines
∼20
nucleotide
spacing
form.
A
structure
ssRNA-bound
shows
how
bridge
dimers
stabilize
structure.
This
tetramer
inactive
respect
RNase
activity.
Nucleic Acids Research,
Год журнала:
2023,
Номер
51(13), С. 7014 - 7024
Опубликована: Май 29, 2023
Abstract
SAMHD1
dNTP
hydrolase
activity
places
it
at
the
crossroad
of
several
important
biological
pathways,
such
as
viral
restriction,
cell
cycle
regulation,
and
innate
immunity.
Recently,
a
dNTPase
independent
function
for
in
homologous
recombination
(HR)
DNA
double-strand
breaks
has
been
identified.
is
regulated
by
post-translational
modifications,
including
protein
oxidation.
Here,
we
showed
that
oxidation
increases
ssDNA
binding
affinity
occurs
cycle-dependent
manner
during
S
phase
consistent
with
role
HR.
We
determined
structure
oxidized
complex
ssDNA.
The
enzyme
binds
regulatory
sites
dimer
interface.
propose
mechanism
acts
functional
switch
to
toggle
between
binding.
Life Science Alliance,
Год журнала:
2024,
Номер
7(11), С. e202402764 - e202402764
Опубликована: Авг. 29, 2024
Mitochondrial
gene
expression
is
a
compartmentalised
process
essential
for
metabolic
function.
The
replication
and
transcription
of
mitochondrial
DNA
(mtDNA)
take
place
at
nucleoids,
whereas
the
subsequent
processing
maturation
RNA
(mtRNA)
mitoribosome
assembly
are
localised
to
granules.
bidirectional
circular
mtDNA
can
lead
hybridisation
polycistronic
transcripts
formation
immunogenic
double-stranded
(mt-dsRNA).
However,
mechanisms
that
regulate
mt-dsRNA
localisation
homeostasis
largely
unknown.
With
super-resolution
microscopy,
we
show
overlaps
with
core
associated
proteins
granules
but
not
nucleoids.
Mt-dsRNA
foci
accumulate
upon
stimulation
cell
proliferation
their
abundance
depends
on
ribonucleotide
supply
by
nucleoside
diphosphate
kinase,
NME6.
Consequently,
profuse
in
cultured
cancer
cells
malignant
human
tumour
biopsies.
Our
results
establish
new
link
between
nucleic
acid
homeostasis.
