International Journal of Molecular Sciences,
Год журнала:
2024,
Номер
25(4), С. 2053 - 2053
Опубликована: Фев. 8, 2024
Heterozygous
variants
in
the
Poly(U)
Binding
Splicing
Factor
60kDa
gene
(PUF60)
have
been
associated
with
Verheij
syndrome,
which
has
key
features
of
coloboma,
short
stature,
skeletal
abnormalities,
developmental
delay,
palatal
and
congenital
heart
kidney
defects.
Here,
we
report
five
novel
patients
from
unrelated
families
PUF60-related
disorders
exhibiting
genetic
clinical
findings
three
truncating
variants,
one
splice-site
variant
likely
reduced
protein
expression,
missense
variant.
Protein
modeling
patient's
PUF60
AlphaFold
structure
revealed
a
loss
polar
bonds
to
surrounding
residues.
Neurodevelopmental
were
present
all
patients,
variability
speech,
motor,
cognitive,
social-emotional
behavioral
features.
Novel
phenotypic
expansions
included
movement
as
well
immunological
recurrent
respiratory,
urinary
ear
infections,
atopic
diseases,
skin
abnormalities.
We
discuss
role
immunity
without
infection
based
on
recent
organismic
cellular
studies.
As
our
showed
less-severe
phenotypes
than
classical
particularly
absence
such
coloboma
or
propose
reclassification
neurodevelopmental
multi-system
involvement.
These
will
aid
counseling
families.
Wiley Interdisciplinary Reviews - RNA,
Год журнала:
2024,
Номер
15(2)
Опубликована: Март 1, 2024
Abstract
Disruptions
in
spatiotemporal
gene
expression
can
result
atypical
brain
function.
Specifically,
autism
spectrum
disorder
(ASD)
is
characterized
by
abnormalities
pre‐mRNA
splicing.
Abnormal
splicing
patterns
have
been
identified
the
brains
of
individuals
with
ASD,
and
mutations
factors
found
to
contribute
neurodevelopmental
delays
associated
ASD.
Here
we
review
studies
that
shed
light
on
importance
observed
ASD
explored
intricate
relationship
between
revealing
how
disruptions
may
underlie
pathogenesis.
We
provide
an
overview
research
regarding
all
place
a
special
emphasis
five
specific
factors—HNRNPH2,
NOVA2,
WBP4,
SRRM2,
RBFOX1—known
impact
ASD‐related
genes.
In
discussion
molecular
mechanisms
influenced
these
factors,
lay
groundwork
for
deeper
understanding
ASD's
complex
etiology.
Finally,
discuss
potential
benefit
unraveling
connection
development
more
precise
diagnostic
tools
targeted
therapeutic
interventions.
This
article
categorized
under:
RNA
Disease
Development
>
Evolution
Genomics
Ribonucleoprotein
Computational
Analyses
RNA‐Based
Catalysis
Splicing
Translation
bioRxiv (Cold Spring Harbor Laboratory),
Год журнала:
2025,
Номер
unknown
Опубликована: Янв. 12, 2025
Abstract
Retroviruses
are
responsible
for
significant
pathology
in
humans
and
animals,
including
the
acquired
immunodeficiency
syndrome
a
wide
range
of
malignancies.
A
crucial
yet
poorly
understood
step
replication
cycle
is
recognition
selection
unspliced
viral
RNA
(USvRNA)
by
retroviral
Gag
protein,
which
binds
to
psi
(Ψ)
packaging
sequence
5’
leader,
package
it
as
genomic
(gRNA)
into
nascent
virions.
It
was
previously
thought
that
initially
bound
gRNA
cytoplasm.
However,
previous
studies
demonstrated
Rous
sarcoma
virus
(RSV)
protein
traffics
transiently
through
nucleus,
necessary
efficient
packaging.
These
data
formed
strong
premise
hypothesis
selects
at
transcription
sites
location
highest
concentration
USvRNA
molecules
cell.
In
support
this
model,
using
fixed
cells
infected
with
RSV
revealed
co-localizes
large
nuclear
foci
representing
transcriptional
burst
sites.
To
test
idea,
we
used
single
molecule
labeling
imaging
techniques
visualize
fluorescently-tagged,
actively
transcribing
genomes,
proteins
living
cells.
condensates
were
observed
co-localized
sites,
forming
co-
localized
ribonucleoprotein
complexes
(vRNPs).
results
novel
paradigm
assembly
interacts
dynamic
kissing
interaction
capture
incorporation
