The
WAVE
regulatory
pentameric
complex
regulates
actin
remodeling.
Two
components
of
it
(CYFIP2
and
NCKAP1)
are
encoded
by
genes
whose
genetic
mutations
increase
the
risk
for
autism
spectrum
disorder
(ASD)
related
neurodevelopmental
disorders.
Here,
we
use
a
newly
developed
computational
protocol
hotspot
analysis
to
uncover
functional
impact
these
at
interface
correct
isoforms
two
proteins
into
complex.
turn
out
be
located
on
surfaces
involving
largest
number
hotspots
Most
them
decrease
affinity
rest
complex,
but
some
have
opposite
effect.
results
fully
consistent
with
available
experimental
data.
observed
changes
in
stability
might
activation
ultimately
play
role
aberrant
pathway
leading
cell
derangement
associated
disease.
International Journal of Molecular Sciences,
Год журнала:
2024,
Номер
25(23), С. 12695 - 12695
Опубликована: Ноя. 26, 2024
Human
genome
projects
in
the
1990s
identified
about
20,000
protein-coding
sequences.
We
are
now
RNA
revolution,
propelled
by
realization
that
genes
determine
phenotype
beyond
foundational
central
molecular
biology
dogma,
stating
inherited
linear
pieces
of
DNA
transcribed
to
RNAs
and
translated
into
proteins.
Crucially,
over
95%
genome,
initially
considered
junk
between
genes,
encodes
essential,
functionally
diverse
non-protein-coding
RNAs,
raising
gene
count
at
least
one
order
magnitude.
Most
phenotype-determining
changes
regulatory
areas
control
can
directly
or
indirectly
phenotypes
regulating
protein
function,
transferring
information
within
organisms,
generating
DNA.
also
exhibit
high
structural,
functional,
biomolecular
interaction
plasticity
modified
via
editing,
methylation,
glycosylation,
other
mechanisms,
which
bestow
them
with
intra-
extracellular
functions
without
altering
underlying
is,
therefore,
currently
primary
determinant
cellular
populational
functional
diversity,
disease-linked
structural
variations,
cell
function
regulation.
As
demonstrated
RNA-based
coronavirus
vaccines'
success,
technology
is
transforming
medicine,
agriculture,
industry,
as
did
advent
recombinant
1980s.
bioRxiv (Cold Spring Harbor Laboratory),
Год журнала:
2024,
Номер
unknown
Опубликована: Ноя. 30, 2024
Achieving
a
diversity
of
neuronal
cell
types
and
circuits
during
brain
development
requires
alternative
splicing
developmentally
regulated
mRNA
transcripts.
Microexons
are
type
alternatively
spliced
exon
that
3-27
nucleotides
in
length
predominantly
expressed
tissues.
A
key
regulator
microexon
is
the
RNA-binding
protein
Serine/arginine
repetitive
matrix
4
(Srrm4).
Srrm4
highly
conserved,
vertebrate
factor
part
an
ancient
family
proteins.
To
better
understand
function
development,
we
examined
neural
expression
zebrafish
srrm4
from
days
1-5
using
fluorescence
situ
hybridization.
We
found
has
dynamically
changing
pattern,
with
diverse
stages
development.
then
used
CRISPR-based
mutagenesis
to
generate
mutants.
Unlike
previously
described
morphant
phenotypes,
mutants
did
not
show
overt
morphological
defects.
Moreover,
sequencing
wild-type
mutant
transcriptomes
revealed
only
minor
changes
splicing.
thus
appears
have
limited
role
The
WAVE
regulatory
pentameric
complex
regulates
actin
remodeling.
Two
components
of
it
(CYFIP2
and
NCKAP1)
are
encoded
by
genes
whose
genetic
mutations
increase
the
risk
for
autism
spectrum
disorder
(ASD)
related
neurodevelopmental
disorders.
Here,
we
use
a
newly
developed
computational
protocol
hotspot
analysis
to
uncover
functional
impact
these
at
interface
correct
isoforms
two
proteins
into
complex.
turn
out
be
located
on
surfaces
involving
largest
number
hotspots
Most
them
decrease
affinity
rest
complex,
but
some
have
opposite
effect.
results
fully
consistent
with
available
experimental
data.
observed
changes
in
stability
might
activation
ultimately
play
role
aberrant
pathway
leading
cell
derangement
associated
disease.
