Nucleic Acids Research,
Год журнала:
2021,
Номер
49(16), С. 9132 - 9153
Опубликована: Авг. 3, 2021
Transposable
elements
(TEs)
occupy
nearly
40%
of
mammalian
genomes
and,
whilst
most
are
fragmentary
and
no
longer
capable
transposition,
they
can
nevertheless
contribute
to
cell
function.
TEs
within
genes
transcribed
by
RNA
polymerase
II
be
copied
as
parts
primary
transcripts;
however,
their
full
contribution
mature
transcript
sequences
remains
unresolved.
Here,
using
long
short
read
(LR
SR)
sequencing
data,
we
show
that
26%
coding
65%
noncoding
transcripts
in
human
pluripotent
stem
cells
(hPSCs)
contain
TE-derived
sequences.
Different
TE
families
incorporated
into
RNAs
unique
patterns,
with
consequences
structure
The
presence
a
is
correlated
TE-type
specific
changes
its
subcellular
distribution,
alterations
steady-state
levels
half-life,
differential
association
Binding
Proteins
(RBPs).
We
identify
hPSC-specific
incorporation
endogenous
retroviruses
(ERVs)
LINE:L1
protein-coding
mRNAs,
which
generate
sequence-derived
peptides.
Finally,
single
RNA-seq
reveals
hPSCs
express
ERV-containing
transcripts,
differentiating
subpopulations
lack
ERVs
SINE
LINE-containing
transcripts.
Overall,
our
comprehensive
analysis
demonstrates
the
more
widespread
has
greater
impact
than
previously
appreciated.
Cell Research,
Год журнала:
2021,
Номер
31(6), С. 613 - 630
Опубликована: Янв. 29, 2021
Organization
of
the
genome
into
euchromatin
and
heterochromatin
appears
to
be
evolutionarily
conserved
relatively
stable
during
lineage
differentiation.
In
an
effort
unravel
basic
principle
underlying
folding,
here
we
focus
on
itself
report
a
fundamental
role
for
L1
(LINE1
or
LINE-1)
B1/Alu
retrotransposons,
most
abundant
subclasses
repetitive
sequences,
in
chromatin
compartmentalization.
We
find
that
homotypic
clustering
demarcates
grossly
exclusive
domains,
characterizes
predicts
Hi-C
compartments.
Spatial
segregation
L1-rich
sequences
nuclear
nucleolar
peripheries
B1/Alu-rich
interior
is
mouse
human
cells
occurs
dynamically
cell
cycle.
addition,
de
novo
establishment
B1
coincident
with
formation
higher-order
structures
early
embryogenesis
critically
regulated
by
transcripts.
Importantly,
depletion
transcripts
embryonic
stem
drastically
weakens
repeat
contacts
compartmental
strength,
disrupts
L1-
B1-rich
chromosomal
at
genome-wide
individual
sites.
Mechanistically,
co-localization
liquid
droplet
DNA
RNA
protein
HP1α
suggest
phase-separation
mechanism
which
promotes
Taken
together,
propose
genetically
encoded
model
repeats
blueprint
macrostructure.
Our
explains
robustness
folding
common
core,
dynamic
gene
regulation
overlaid
across
cells.
Cancer Discovery,
Год журнала:
2021,
Номер
11(11), С. 2707 - 2725
Опубликована: Окт. 14, 2021
Abstract
Features
of
the
cancer
epigenome
distinguish
cancers
from
their
respective
cell
origin
and
establish
therapeutic
vulnerabilities
that
can
be
exploited
through
pharmacologic
inhibition
DNA-
or
histone-modifying
enzymes.
Epigenetic
therapies
converge
with
immunotherapies
“viral
mimicry,”
a
cellular
state
active
antiviral
response
triggered
by
endogenous
nucleic
acids
often
derived
aberrantly
transcribed
retrotransposons.
This
review
describes
initial
characterization
expansion
viral
mimicry–inducing
approaches
as
well
features
“prime”
for
mimicry
induction.
Increased
understanding
in
contexts
suggests
potential
physiologic
roles
homeostasis.
Significance:
Recent
literature
establishes
elevated
cytosolic
double
strand
RNA
(dsRNA)
levels
cancer-specific
vulnerability
beyond
tolerable
thresholds
to
induce
signaling
increase
dependence
on
dsRNA
stress
responses
mediated
ADAR1.
Improved
tolerance
mechanisms
reveals
synergistic
treatment
combinations
epigenetic
include
BCL2,
ADAR1,
immune
checkpoint
blockade.
Further
may
identify
maximize
efficacy
conventional
therapies.
Protein & Cell,
Год журнала:
2021,
Номер
12(6), С. 455 - 474
Опубликована: Апрель 22, 2021
Abstract
N
6
-methyladenosine
(m
A)
on
chromosome-associated
regulatory
RNAs
(carRNAs),
including
repeat
RNAs,
plays
important
roles
in
tuning
the
chromatin
state
and
transcription,
but
intrinsic
mechanism
remains
unclear.
Here,
we
report
that
YTHDC1
indispensable
self-renewal
differentiation
potency
of
mouse
embryonic
stem
cells
(ESCs),
which
highly
depends
m
A-binding
ability.
Ythdc1
is
required
for
sufficient
rRNA
synthesis
repression
2-cell
(2C)
transcriptional
program
ESCs,
recapitulates
transcriptome
regulation
by
LINE1
scaffold.
Detailed
analyses
revealed
recognizes
A
nucleus
regulates
formation
LINE1-NCL
partnership
recruitment
KAP1.
Moreover,
establishment
H3K9me3
2C-related
retrotransposons
interrupted
-depleted
ESCs
inner
cell
mass
(ICM)
cells,
consequently
increases
activities.
Our
study
reveals
a
role
regulating
RNA
scaffold,
providing
new
model
RNA-chromatin
cross-talk.
Nature Communications,
Год журнала:
2023,
Номер
14(1)
Опубликована: Апрель 14, 2023
Abstract
Although
more
studies
are
demonstrating
that
a
father’s
environment
can
influence
child
health
and
disease,
the
molecular
mechanisms
underlying
non-genetic
inheritance
remain
unclear.
It
was
previously
thought
sperm
exclusively
contributed
its
genome
to
egg.
More
recently,
association
have
shown
various
environmental
exposures
including
poor
diet,
toxicants,
stress,
perturbed
epigenetic
marks
in
at
important
reproductive
developmental
loci
were
associated
with
offspring
phenotypes.
The
cellular
routes
underlie
how
transmitted
fertilization,
resist
reprogramming
embryo,
drive
phenotypic
changes
only
now
beginning
be
unraveled.
Here,
we
provide
an
overview
of
state
field
intergenerational
paternal
mammals
present
new
insights
into
relationship
between
embryo
development
three
pillars
inheritance:
chromatin,
DNA
methylation,
non-coding
RNAs.
We
evaluate
compelling
evidence
sperm-mediated
transmission
retention
embryo.
Using
landmark
examples,
discuss
sperm-inherited
regions
may
escape
impact
via
implicate
transcription
factors,
chromatin
organization,
transposable
elements.
Finally,
link
paternally
functional
pre-
post-implantation
Understanding
factors
will
permit
greater
understanding
related
origins
disease.
Cell Reports,
Год журнала:
2021,
Номер
36(6), С. 109500 - 109500
Опубликована: Авг. 1, 2021
Loss
of
function
adenosine
deaminase
acting
on
double-stranded
RNA
(dsRNA)-1
(ADAR1)
causes
the
severe
autoinflammatory
disease
Aicardi-Goutières
syndrome
(AGS).
ADAR1
converts
adenosines
into
inosines
within
dsRNA.
This
process
called
A-to-I
editing
masks
self-dsRNA
from
detection
by
antiviral
dsRNA
sensor
MDA5.
binds
to
in
both
canonical
A-form
and
poorly
defined
Z
conformation
(Z-RNA).
Mutations
Z-RNA-binding
Zα
domain
are
common
patients
with
AGS.
How
loss
ADAR1/Z-RNA
interaction
contributes
development
is
unknown.
We
demonstrate
that
abrogated
binding
Z-RNA
leads
reduced
structures
formed
base
pairing
inversely
oriented
short
interspersed
nuclear
elements.
Preventing
triggers
an
MDA5/MAVS-mediated
type
I
interferon
response
lethal
autoinflammation
mice.
shows
between
restricts
sensing
prevents
AGS
development.
