RNA Polymerase II Activity Control of Gene Expression and Involvement in Disease
Journal of Molecular Biology,
Год журнала:
2024,
Номер
437(1), С. 168770 - 168770
Опубликована: Авг. 28, 2024
Gene
expression
is
dependent
on
RNA
Polymerase
II
(Pol
II)
activity
in
eukaryotes.
In
addition
to
determining
the
rate
of
synthesis
for
all
protein
coding
genes,
Pol
serves
as
a
platform
recruitment
factors
and
regulation
co-transcriptional
events,
from
processing
chromatin
modification
remodeling.
The
transcriptome
can
be
shaped
by
changes
kinetics
affecting
itself
or
because
alterations
events
that
are
responsive
coupled
with
transcription.
Genetic,
biochemical,
structural
approaches
model
organisms
have
revealed
critical
insights
into
how
works
types
regulate
it.
complexity
generally
increases
organismal
complexity.
this
review,
we
describe
fundamental
aspects
shape
gene
expression,
discuss
recent
advances
elongation
regulated
altered
function
linked
human
disease
aging.
Язык: Английский
Next-Generation Mapping of the ACINUS-Mediated Alternative Splicing Machinery and Its Regulation by O-glycosylation inArabidopsis
bioRxiv (Cold Spring Harbor Laboratory),
Год журнала:
2025,
Номер
unknown
Опубликована: Янв. 4, 2025
Alternative
splicing
(AS)
is
a
key
mechanism
of
gene
regulation,
but
the
full
repertoire
proteins
involved
and
regulatory
mechanisms
governing
this
process
remain
poorly
understood.
Using
TurboID-based
proximity
labeling
coupled
with
mass
spectrometry
(PL-MS),
we
comprehensively
mapped
Arabidopsis
AS
machinery,
focusing
on
evolutionarily
conserved
factor
ACINUS,
its
paralog
PININ,
stable
interactor
SR45.
We
identified
298
high-confidence
components,
including
both
established
novel
interactors,
providing
strong
evidence
that
alternative
to
transcription
multiple
RNA
processing
steps
occur
simultaneously
in
plants.
Bioinformatic
analysis
reveals
high
redundancy,
mechanisms,
unique
plant-specific
features.
Selected
known
interactors
were
validated
by
readouts
phenotypic
analysis,
which
also
revealed
coordinated
influence
splicing.
Furthermore,
systematic
evaluation
O-glycosylation
double
mutants
SECRET
AGENT
(O-GlcNAc
transferase)
SPINDLY
(O-fucose
modulate
through
ACINUS-dependent
-independent
pathways.
Our
results
reveal
as
well
network
highlight
global
role
sugar
modification
processing.
Язык: Английский
PAF1C-mediated activation of CDK12/13 kinase activity is critical for CTD phosphorylation and transcript elongation
Molecular Cell,
Год журнала:
2025,
Номер
unknown
Опубликована: Май 1, 2025
The
transcription
cycle
is
regulated
by
dynamic
changes
in
RNA
polymerase
II
(RNAPII)
C-terminal
domain
(CTD)
phosphorylation,
which
are
crucial
for
gene
expression.
However,
the
mechanisms
regulating
transcription-specific
cyclin-dependent
kinases
(CDKs)
during
remain
poorly
understood.
Here,
we
show
that
human
CDK12
co-phosphorylates
CTD
Serine2
and
Serine5.
This
di-phosphorylated
Serine2-Serine5
mark
may
then
act
as
a
precursor
mono-phosphorylated
through
Serine5
de-phosphorylation.
Notably,
specifically
association
with
elongation-specific
factor
PAF1
complex
(PAF1C),
CDC73
subunit
contains
metazoan-specific
peptide
motif,
capable
of
allosteric
CDK12/cyclin
K
activation.
motif
essential
cell
proliferation
required
normal
levels
phosphorylation
chromatin,
transcript
elongation,
particularly
across
long
genes.
Together,
these
findings
provide
insight
into
governing
RNAPII
phospho-CTD
dynamics
ensure
progression
cycle.
Язык: Английский
High-resolution sequencing reveals that the Paf1 complex may be a conserved transcription elongation factor for eukaryotic RNA polymerase I
Journal of Molecular Biology,
Год журнала:
2025,
Номер
unknown, С. 169220 - 169220
Опубликована: Май 1, 2025
Язык: Английский
A direct interaction between the Chd1 CHCT domain and Rtf1 controls Chd1 distribution and nucleosome positioning on active genes
bioRxiv (Cold Spring Harbor Laboratory),
Год журнала:
2024,
Номер
unknown
Опубликована: Дек. 6, 2024
ABSTRACT
The
nucleosome
remodeler
Chd1
is
required
for
the
re-establishment
of
positioning
in
wake
transcription
elongation
by
RNA
Polymerase
II.
Previously,
we
found
that
occupancy
on
gene
bodies
depends
Rtf1
subunit
Paf1
complex
yeast.
Here,
identify
an
N-terminal
region
and
CHCT
domain
as
sufficient
their
interaction
demonstrate
this
direct.
Mutations
disrupt
Rtf1-Chd1
result
accumulation
at
5’
ends
Chd1-occupied
genes,
increased
cryptic
transcription,
altered
positioning,
concordant
shifts
histone
modification
profiles.
We
show
a
homologous
within
mouse
RTF1
interacts
with
domains
CHD1
CHD2.
This
work
supports
conserved
mechanism
coupling
family
proteins
to
identifies
cellular
function
about
which
little
known.
Язык: Английский
The DNA damage response and RNA Polymerase II regulator Def1 has posttranscriptional functions in the cytoplasm
bioRxiv (Cold Spring Harbor Laboratory),
Год журнала:
2024,
Номер
unknown
Опубликована: Сен. 16, 2024
Abstract
Yeast
Def1
mediates
RNA
polymerase
II
degradation
and
transcription
elongation
during
stress.
is
predominantly
cytoplasmic,
DNA
damage
signals
cause
its
proteolytic
processing,
liberating
N-terminus
to
enter
the
nucleus.
Cytoplasmic
functions
for
this
abundant
protein
have
not
been
identified.
Proximity-labeling
(BioID)
experiments
indicate
that
binds
an
array
of
proteins
involved
in
posttranscriptional
control
translation
mRNAs.
Deleting
DEF1
reduces
both
mRNA
synthesis
decay
rates,
indicating
transcript
buffering
mutant.
Directly
tethering
a
reporter
suppressed
expression,
suggesting
directly
regulates
Surprisingly,
we
found
interacts
with
polyribosomes,
which
requires
ubiquitin-binding
domain
located
N-terminus.
The
binding
ribosomes
ubiquitylation
eS7a
(Rsp7A)
small
subunit
by
Not4
Ccr4-Not
complex.
ribosome
quality
co-translational
decay.
polyglutamine-rich
unstructured
C-terminus
required
interaction
factors,
acts
as
ubiquitin-dependent
scaffold
link
status
Thus,
identified
novel
function
response
factor
regulation
cytoplasm
establish
master
regulator
gene
functioning
transcription,
decay,
translation.
Язык: Английский