The EMBO Journal,
Journal Year:
2023,
Volume and Issue:
42(8)
Published: Feb. 27, 2023
The
failure
to
repress
transcription
of
repetitive
genomic
elements
can
lead
catastrophic
genome
instability
and
is
associated
with
various
human
diseases.
As
such,
multiple
parallel
mechanisms
cooperate
ensure
repression
heterochromatinization
these
elements,
especially
during
germline
development
early
embryogenesis.
A
vital
question
in
the
field
how
specificity
establishing
heterochromatin
at
achieved.
Apart
from
trans-acting
protein
factors,
recent
evidence
points
a
role
different
RNA
species
targeting
repressive
histone
marks
DNA
methylation
sites
mammals.
Here,
we
review
discoveries
on
this
topic
predominantly
focus
methylation,
piRNAs,
other
localized
satellite
RNAs.
Molecular Cell,
Journal Year:
2022,
Volume and Issue:
82(9), P. 1691 - 1707.e8
Published: March 28, 2022
Transposable
elements
(TEs)
are
widespread
genetic
parasites
known
to
be
kept
under
tight
transcriptional
control.
Here,
we
describe
a
functional
connection
between
the
mouse-orthologous
"nuclear
exosome
targeting"
(NEXT)
and
"human
silencing
hub"
(HUSH)
complexes,
involved
in
nuclear
RNA
decay
epigenetic
of
TEs,
respectively.
Knocking
out
NEXT
component
ZCCHC8
embryonic
stem
cells
results
elevated
TE
levels.
We
identify
physical
interaction
MPP8
protein
HUSH
establish
that
recruits
chromatin
at
MPP8-bound
loci.
However,
while
both
dampen
expression,
their
activities
predominantly
affect
shorter
non-polyadenylated
full-length
polyadenylated
transcripts,
Indeed,
our
data
suggest
repressive
action
promotes
condition
favoring
activity.
In
this
way,
post-transcriptional
machineries
synergize
suppress
genotoxic
potential
RNAs.
Nature,
Journal Year:
2024,
Volume and Issue:
626(8001), P. 1116 - 1124
Published: Feb. 14, 2024
Abstract
Transposable
elements
(TEs)
are
a
major
constituent
of
human
genes,
occupying
approximately
half
the
intronic
space.
During
pre-messenger
RNA
synthesis,
TEs
transcribed
along
with
their
host
genes
but
rarely
contribute
to
final
mRNA
product
because
they
spliced
out
together
intron
and
rapidly
degraded.
Paradoxically,
an
abundant
source
RNA-processing
signals
through
which
can
create
new
introns
1
,
also
functional
2
or
non-functional
chimeric
transcripts
3
.
The
rarity
these
events
implies
existence
resilient
splicing
code
that
is
able
suppress
TE
exonization
without
compromising
pre-mRNA
processing.
Here
we
show
SAFB
proteins
protect
genome
integrity
by
preventing
retrotransposition
L1
while
maintaining
integrity,
via
prevention
previously
integrated
TEs.
This
unique
dual
role
possible
L1’s
conserved
adenosine-rich
coding
sequences
bound
proteins.
suppressive
activity
extends
tissue-specific,
giant
protein-coding
cassette
exons,
nested
Tigger
DNA
transposons.
Moreover,
suppresses
LTR/ERV
in
species
still
active,
such
as
mice
flies.
A
significant
subset
suppressed
somatic
cells
activated
testis,
coinciding
low
expression
postmeiotic
spermatids.
Reminiscent
division
labour
between
innate
adaptive
immune
systems
fight
external
pathogens,
our
results
uncover
RNA-based,
pattern-guided,
non-adaptive
defence
system
against
soma,
complementing
Piwi-interacting
pathway
germline.
Trends in Genetics,
Journal Year:
2023,
Volume and Issue:
39(4), P. 251 - 267
Published: Feb. 6, 2023
The
vertebrate
genome
is
under
constant
threat
of
invasion
by
genetic
parasites.
Whether
the
host
can
immediately
recognize
and
respond
to
invading
elements
has
been
unclear.
discovery
human
silencing
hub
(HUSH)
complex,
finding
that
it
provides
immediate
protection
from
products
reverse
transcription,
have
important
implications
for
mammalian
evolution.
In
this
review,
we
summarize
recent
insights
into
HUSH
function
describe
how
cellular
introns
provide
a
novel
means
self–nonself
discrimination,
allowing
transcriptionally
repress
broad
range
intronless
elements.
We
discuss
contributes
evolution,
highlight
studies
reporting
critical
role
in
development
implicating
control
immune
signaling
cancer
progression.
Genome Research,
Journal Year:
2023,
Volume and Issue:
33(8), P. 1409 - 1423
Published: Aug. 1, 2023
Krüppel-associated
box
(KRAB)
domain-containing
zinc
finger
proteins
(KZFPs)
are
one
of
the
largest
groups
transcription
factors
encoded
by
tetrapods,
with
378
members
in
human
alone.
KZFP
genes
often
grouped
clusters
reflecting
amplification
gene
and
segment
duplication
since
family
first
emerged
more
than
400
million
years
ago.
Previous
work
has
revealed
that
many
KZFPs
recognize
transposable
element
(TE)-embedded
sequences
as
genomic
targets,
facilitate
co-option
regulatory
potential
TEs
for
benefit
host.
Here,
we
present
a
comprehensive
survey
genetic
features
targets
KZFPs,
notably
completing
past
analyses
adding
data
on
close
to
hundred
members.
General
principles
emerge
from
our
study
TE-KZFP
system,
which
point
multipronged
evolutionary
mechanisms
underlaid
highly
complex
combinatorial
modes
action
strong
influences
speciation.
Molecular Cell,
Journal Year:
2023,
Volume and Issue:
83(10), P. 1623 - 1639.e8
Published: May 1, 2023
The
HUSH
complex
recognizes
and
silences
foreign
DNA
such
as
viruses,
transposons,
transgenes
without
prior
exposure
to
its
targets.
Here,
we
show
that
endogenous
targets
of
the
fall
into
two
distinct
classes
based
on
presence
or
absence
H3K9me3.
These
are
further
distinguished
by
their
transposon
content
differential
response
loss
HUSH.
A
de
novo
genomic
rearrangement
at
Sox2
locus
induces
a
switch
from
H3K9me3-independent
H3K9me3-associated
targeting,
resulting
in
silencing.
We
demonstrate
interacts
with
termination
factor
WDR82
and—via
component
MPP8—with
nascent
RNA.
accumulates
sites
high
RNAPII
occupancy
including
long
exons
transcription
manner
dependent
CPSF.
Together,
our
results
uncover
functional
diversity
this
vertebrate-specific
exploits
evolutionarily
ancient
machinery
for
co-transcriptional
chromatin
targeting
genome
surveillance.
Genes & Development,
Journal Year:
2023,
Volume and Issue:
37(21-24), P. 948 - 967
Published: Nov. 1, 2023
Long
interspersed
element
1
(LINE-1)
is
the
only
protein-coding
transposon
that
active
in
humans.
LINE-1
propagates
genome
using
RNA
intermediates
via
retrotransposition.
This
activity
has
resulted
sequences
occupying
approximately
one-fifth
of
our
genome.
Although
most
copies
are
immobile,
∼100
retrotransposition-competent.
Retrotransposition
normally
limited
epigenetic
silencing,
DNA
repair,
and
other
host
defense
mechanisms.
In
contrast,
overexpression
retrotransposition
hallmarks
cancers.
Here,
we
review
mechanisms
regulation
how
may
promote
genetic
heterogeneity
tumors.
Finally,
discuss
therapeutic
strategies
to
exploit
biology
