Nature Plants,
Journal Year:
2022,
Volume and Issue:
8(4), P. 402 - 418
Published: April 21, 2022
In
most
organisms,
the
maturation
of
nascent
RNAs
is
coupled
to
transcription.
Unlike
in
animals,
RNA
polymerase
II
(RNAPII)
transcribes
microRNA
genes
(MIRNAs)
as
long
and
structurally
variable
pri-miRNAs
plants.
Current
evidence
suggests
that
miRNA
biogenesis
complex
assembly
initiates
early
during
transcription
However,
it
unknown
whether
processing
occurs
co-transcriptionally.
Here,
we
used
native
elongating
transcript
sequencing
data
imaging
techniques
demonstrate
plant
We
found
entire
co-transcriptionally
for
processed
from
loop
hairpin
but
requires
a
second
nucleoplasmic
step
those
base.
Furthermore,
co-
post-transcriptional
mechanisms
co-exist
miRNAs
dynamic
balance.
Notably,
discovered
R-loops,
formed
near
start
site
region
MIRNAs,
promote
co-transcriptional
pri-miRNA
processing.
our
results
suggest
neofunctionalization
miRNAs,
boosting
countless
regulatory
scenarios.
Nature Communications,
Journal Year:
2021,
Volume and Issue:
12(1)
Published: Dec. 16, 2021
Transcription
poses
a
threat
to
genomic
stability
through
the
formation
of
R-loops
that
can
obstruct
progression
replication
forks.
are
three-stranded
nucleic
acid
structures
formed
by
an
RNA-DNA
hybrid
with
displaced
non-template
DNA
strand.
We
developed
Proximity
Proteomics
map
R-loop
proximal
proteome
human
cells
using
quantitative
mass
spectrometry.
implicate
different
cellular
proteins
in
regulation
and
identify
role
tumor
suppressor
DDX41
opposing
double
strand
break
accumulation
promoters.
is
enriched
promoter
regions
vivo,
unwind
hybrids
vitro.
upon
loss
accompanied
stress,
increase
breaks
transcriptome
changes
associated
inflammatory
response.
Germline
loss-of-function
mutations
lead
predisposition
acute
myeloid
leukemia
adulthood.
propose
instability-associated
response
may
contribute
development
familial
AML
mutated
DDX41.
Nature Communications,
Journal Year:
2022,
Volume and Issue:
13(1)
Published: Jan. 10, 2022
Abstract
R-loops
are
three-stranded
nucleic
acid
structures
that
accumulate
on
chromatin
in
neurological
diseases
and
cancers
contribute
to
genome
instability.
Using
a
proximity-dependent
labeling
system,
we
identified
distinct
classes
of
proteins
regulate
vivo
through
different
mechanisms.
We
show
ATRX
suppresses
by
interacting
with
RNAs
preventing
R-loop
formation.
Our
proteomics
screen
also
discovered
an
unexpected
enrichment
for
containing
zinc
fingers
homeodomains.
One
the
most
consistently
enriched
was
activity-dependent
neuroprotective
protein
(ADNP),
which
is
frequently
mutated
ASD
causal
ADNP
syndrome.
find
resolves
vitro
it
necessary
suppress
at
its
genomic
targets.
Furthermore,
deletion
homeodomain
severely
diminishes
resolution
activity
vitro,
results
accumulation
targets,
compromises
neuronal
differentiation.
Notably,
patient-derived
human
induced
pluripotent
stem
cells
contain
syndrome-causing
mutation
exhibit
CTCF
findings
point
specific
role
ADNP-mediated
physiological
pathological
function
and,
more
broadly,
finger
regulation,
important
implications
developmental
disorders
cancers.