Nucleic Acids Research,
Год журнала:
2024,
Номер
unknown
Опубликована: Дек. 24, 2024
Abstract
Defining
the
beginning
of
a
eukaryotic
protein-coding
gene
is
relatively
simple.
It
corresponds
to
first
ribonucleotide
incorporated
by
RNA
polymerase
II
(Pol
II)
into
nascent
molecule.
This
nucleotide
protected
capping
and
maintained
in
mature
messenger
(mRNA).
However,
higher
eukaryotes,
end
mRNA
separated
from
sites
transcription
termination
hundreds
thousands
base
pairs.
Currently
used
genomic
annotations
only
take
account
transcript
–
where
pre-mRNA
cleavage
occurs,
while
regions
which
terminates
are
unannotated.
Here,
we
describe
evidence
for
marker
termination,
could
be
widely
applicable
studies.
Pol
can
determined
genome-wide
detecting
phosphorylated
on
threonine
4
its
C-terminal
domain
CTD-T4ph).
this
state
pauses
before
leaving
DNA
template.
Up
date
potent
mark
has
been
underused
because
place
role
scattered
across
multiple
publications.
We
summarize
observations
regarding
CTD-T4ph
present
bioinformatic
analyses
that
further
support
as
global
animals.
Molecular Systems Biology,
Год журнала:
2025,
Номер
unknown
Опубликована: Март 31, 2025
Abstract
The
general
transcription
machinery
and
its
occupancy
at
promoters
are
highly
conserved
across
metazoans.
This
contrasts
with
the
kinetics
of
mRNA
production
that
considerably
differ
between
model
species
such
as
Drosophila
mouse.
molecular
basis
for
these
kinetic
differences
is
currently
unknown.
Here,
we
used
Single-Molecule
Footprinting
to
measure
RNA
Polymerase
II
(Pol
II)
occupancy,
fraction
DNA
molecules
bound,
in
mouse
cell
lines.
Single-molecule
data
reveals
Pol
on
average
3–5
times
more
frequent
transcriptionally
active
than
promoters.
Kinetic
modelling
states
suggests
determined
by
ratio
initiation
turnover
rates.
We
chemical
perturbation
determine
rate
both
species.
Integration
into
shows
infrequent
explained
combination
high
low
Nucleic Acids Research,
Год журнала:
2024,
Номер
52(21), С. 13036 - 13056
Опубликована: Окт. 24, 2024
Abstract
DNA
double-strand
breaks
(DSBs)
represent
a
lethal
form
of
damage
that
can
trigger
cell
death
or
initiate
oncogenesis.
The
activity
RNA
polymerase
II
(RNAPII)
at
the
break
site
is
required
for
efficient
DSB
repair.
However,
regulatory
mechanisms
governing
transcription
cycle
DSBs
are
not
well
understood.
Here,
we
show
Integrator
complex
subunit
6
(INTS6)
associates
with
heterotrimeric
sensor
ssDNA
(SOSS1)
(comprising
INTS3,
INIP
and
hSSB1)
to
tetrameric
SOSS1
complex.
INTS6
binds
DNA:RNA
hybrids
promotes
Protein
Phosphatase
2A
(PP2A)
recruitment
DSBs,
facilitating
dephosphorylation
RNAPII.
Furthermore,
prevents
accumulation
damage-associated
transcripts
(DARTs)
stabilization
sites.
interacts
senataxin
(SETX)
resolution
hybrids/R-loops.
Our
results
underscore
significance
in
autoregulation
