The American Journal of Human Genetics,
Год журнала:
2024,
Номер
111(5), С. 913 - 926
Опубликована: Апрель 15, 2024
Expanded
CAG
repeats
in
coding
regions
of
different
genes
are
the
most
common
cause
dominantly
inherited
spinocerebellar
ataxias
(SCAs).
These
unstable
through
germline,
and
larger
lead
to
earlier
onset.
We
measured
somatic
expansion
blood
samples
collected
from
30
SCA1,
50
SCA2,
74
SCA3,
SCA7
individuals
over
a
mean
interval
8.5
years,
along
with
postmortem
tissues
fetal
examine
at
stages
life.
showed
that
mosaicism
increases
time.
Expansion
levels
significantly
among
SCAs
correlate
repeat
lengths.
The
level
is
greater
who
manifest
disease
compared
those
do
not
yet
display
symptoms.
Brain
SCA
have
expansions
blood.
cerebellum
has
lowest
studied
brain
regions,
high
expression
ATXNs
DNA
repair
genes.
This
was
opposite
cortices,
highest
lower
Fetal
cortices
did
show
instability.
study
shows
increasingly
during
life
individuals,
gene-
tissue-specific
patterns.
Communications Biology,
Год журнала:
2023,
Номер
6(1)
Опубликована: Сен. 19, 2023
Abstract
Repetitive
DNA
sequences
playing
critical
roles
in
driving
evolution,
inducing
variation,
and
regulating
gene
expression.
In
this
review,
we
summarized
the
definition,
arrangement,
structural
characteristics
of
repeats.
Besides,
introduced
diverse
biological
functions
repeats
reviewed
existing
methods
for
automatic
repeat
detection,
classification,
masking.
Finally,
analyzed
type,
structure,
regulation
human
genome
their
role
induction
complex
diseases.
We
believe
that
review
will
facilitate
a
comprehensive
understanding
provide
guidance
annotation
in-depth
exploration
its
association
with
Signal Transduction and Targeted Therapy,
Год журнала:
2023,
Номер
8(1)
Опубликована: Авг. 24, 2023
The
proper
transfer
of
genetic
information
from
DNA
to
RNA
protein
is
essential
for
cell-fate
control,
development,
and
health.
Methylation
DNA,
RNAs,
histones,
non-histone
proteins
a
reversible
post-synthesis
modification
that
finetunes
gene
expression
function
in
diverse
physiological
processes.
Aberrant
methylation
caused
by
mutations
or
environmental
stimuli
promotes
various
diseases
accelerates
aging,
necessitating
the
development
therapies
correct
disease-driver
imbalance.
In
this
Review,
we
summarize
operating
system
across
central
dogma,
which
includes
writers,
erasers,
readers,
reader-independent
outputs.
We
then
discuss
how
dysregulation
contributes
neurological
disorders,
cancer,
aging.
Current
small-molecule
compounds
target
modifiers
show
modest
success
certain
cancers.
methylome-wide
action
lack
specificity
lead
undesirable
biological
effects
cytotoxicity,
limiting
their
therapeutic
application,
especially
with
monogenic
cause
different
directions
changes.
Emerging
tools
capable
site-specific
manipulation
hold
great
promise
solve
dilemma.
With
refinement
delivery
vehicles,
these
new
are
well
positioned
advance
basic
research
clinical
translation
field.
Experimental & Molecular Medicine,
Год журнала:
2024,
Номер
56(6), С. 1272 - 1280
Опубликована: Июнь 14, 2024
Abstract
Circular
RNAs
(circRNAs)
are
covalently
closed
single-stranded
without
a
5′
cap
structure
and
3′
poly(A)
tail
typically
present
in
linear
mRNAs
of
eukaryotic
cells.
CircRNAs
predominantly
generated
through
back-splicing
process
within
the
nucleus.
have
long
been
considered
non-coding
seemingly
devoid
protein-coding
potential.
However,
many
recent
studies
challenged
this
idea
provided
substantial
evidence
that
subset
circRNAs
can
associate
with
polysomes
indeed
be
translated.
Therefore,
review,
we
primarily
highlight
5’
cap-independent
internal
initiation
translation
occurs
on
circular
RNAs.
Several
molecular
features
circRNAs,
including
ribosome
entry
site,
N
6
-methyladenosine
modification,
exon
junction
complex
deposited
around
after
event,
play
pivotal
roles
their
efficient
translation.
We
also
propose
possible
relationship
between
translatability
stability,
focus
nonsense-mediated
mRNA
decay
nonstop
decay,
both
which
well-characterized
surveillance
mechanisms.
An
in-depth
understanding
circRNA
will
reshape
expand
our
current
knowledge
proteomics.
Neuron,
Год журнала:
2022,
Номер
110(7), С. 1173 - 1192.e7
Опубликована: Фев. 2, 2022
In
Huntington's
disease
(HD),
the
uninterrupted
CAG
repeat
length,
but
not
polyglutamine
predicts
onset.
However,
underlying
pathobiology
remains
unclear.
Here,
we
developed
bacterial
artificial
chromosome
(BAC)
transgenic
mice
expressing
human
mutant
huntingtin
(mHTT)
with
uninterrupted,
and
somatically
unstable,
repeats
that
exhibit
progressive
disease-related
phenotypes.
Unlike
prior
mHTT
models
stable,
CAA-interrupted,
polyglutamine-encoding
repeats,
BAC-CAG
show
robust
striatum-selective
nuclear
inclusions
transcriptional
dysregulation
resembling
those
in
murine
knockin
HD
patients.
Importantly,
striatal
transcriptionopathy
is
significantly
correlated
their
length
length.
Finally,
among
pathogenic
entities
originating
from
genomic
transgenes
only
present
or
enriched
model,
somatic
instability
aggregation
are
best
early-onset
molecular
pathogenesis
locomotor
sleep
deficits,
while
RNA-associated
pathologies
repeat-associated
non-AUG
(RAN)
translation
may
play
less
selective
late
roles,
respectively.
Nature,
Год журнала:
2023,
Номер
623(7987), С. 580 - 587
Опубликована: Ноя. 8, 2023
Abstract
Microsatellite
repeat
expansions
within
genes
contribute
to
a
number
of
neurological
diseases
1,2
.
The
accumulation
toxic
proteins
and
RNA
molecules
with
repetitive
sequences,
and/or
sequestration
RNA-binding
by
containing
expanded
repeats
are
thought
be
important
contributors
disease
aetiology
3–9
Here
we
reveal
that
the
adenosine
in
CAG
can
methylated
N
1
-methyladenosine
(m
A)
TRMT61A,
m
A
demethylated
ALKBH3.
We
also
observed
A/adenosine
ratio
increases
length,
which
is
attributed
diminished
expression
ALKBH3
elicited
RNA.
Additionally,
TDP-43
binds
directly
strongly
RNA,
stimulates
cytoplasmic
mis-localization
formation
gel-like
aggregates
TDP-43,
resembling
observations
made
for
protein
diseases.
Moreover,
contributes
expansion-induced
neurodegeneration
Caenorhabditis
elegans
Drosophila
In
sum,
our
study
offers
new
paradigm
mechanism
through
nucleotide
expansion
reveals
novel
pathological
function
These
findings
may
provide
an
mechanistic
basis
therapeutic
intervention
neurodegenerative
emanating
from
expansion.
