Current Opinion in Genetics & Development,
Journal Year:
2023,
Volume and Issue:
82, P. 102092 - 102092
Published: July 28, 2023
Transposable
elements
(TEs)
are
ubiquitous
among
eukaryotic
species.
Their
evolutionary
persistence
is
likely
due
to
a
combination
of
tolerogenic,
evasive/antagonistic,
and
cooperative
interactions
with
their
host
genomes.
Here,
we
focus
on
metazoan
species
review
recent
advances
related
the
harmful
effects
TE
insertions,
including
how
epigenetic
TE-derived
RNAs
can
damage
cells.
We
discuss
new
findings
pathways
that
silence
TEs,
such
as
piRNA
pathway
APOBEC3
Kruppel-associated
box
zinc
finger
gene
families.
Finally,
summarize
novel
strategies
used
by
TEs
evade
silencing,
Y
chromosome
permissive
niche
for
mobilization
counterdefense
block
silencing
factors.
Signal Transduction and Targeted Therapy,
Journal Year:
2023,
Volume and Issue:
8(1)
Published: March 14, 2023
Abstract
The
ageing
process
is
a
systemic
decline
from
cellular
dysfunction
to
organ
degeneration,
with
more
predisposition
deteriorated
disorders.
Rejuvenation
refers
giving
aged
cells
or
organisms
youthful
characteristics
through
various
techniques,
such
as
reprogramming
and
epigenetic
regulation.
great
leaps
in
rejuvenation
prove
that
not
one-way
street,
many
rejuvenative
interventions
have
emerged
delay
even
reverse
the
process.
Defining
mechanism
by
which
roadblocks
signaling
inputs
influence
complex
programs
essential
for
understanding
developing
strategies.
Here,
we
discuss
intrinsic
extrinsic
factors
counteract
cell
rejuvenation,
targeted
core
mechanisms
involved
this
Then,
critically
summarize
latest
advances
state-of-art
strategies
of
rejuvenation.
Various
methods
also
provide
insights
treating
specific
ageing-related
diseases,
including
reprogramming,
removal
senescence
(SCs)
suppression
senescence-associated
secretory
phenotype
(SASP),
metabolic
manipulation,
stem
cells-associated
therapy,
dietary
restriction,
immune
heterochronic
transplantation,
etc.
potential
applications
therapy
extend
cancer
treatment.
Finally,
analyze
detail
therapeutic
opportunities
challenges
technology.
Deciphering
will
further
into
anti-ageing
disease
treatment
clinical
settings.
Nucleic Acids Research,
Journal Year:
2024,
Volume and Issue:
52(5), P. 2648 - 2671
Published: Jan. 5, 2024
Abstract
Telomerase-negative
tumors
maintain
telomere
length
by
alternative
lengthening
of
telomeres
(ALT),
but
the
underlying
mechanism
behind
ALT
remains
poorly
understood.
A
proportion
aggressive
neuroblastoma
(NB),
particularly
relapsed
tumors,
are
positive
for
(ALT+),
suggesting
that
a
better
dissection
could
lead
to
novel
therapeutic
opportunities.
TERRA,
long
non-coding
RNA
(lncRNA)
derived
from
ends,
localizes
in
R-loop-dependent
manner
and
plays
crucial
role
maintenance.
Here
we
present
evidence
modification
at
N6
position
internal
adenosine
(m6A)
TERRA
methyltransferase
METTL3
is
essential
maintenance
ALT+
cells,
loss
m6A/METTL3
results
damage.
We
observed
m6A
abundant
R-loop
enriched
m6A-mediated
recruitment
hnRNPA2B1
critical
formation.
Our
findings
suggest
drives
targeting
via
R-loops,
this
formation
be
widespread
employed
other
chromatin-interacting
lncRNAs.
Furthermore,
treatment
NB
cells
with
inhibitor
resulted
compromised
accumulation
DNA
damage
telomeres,
indicating
inhibition
may
represent
approach
NB.
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.
