Scientific Reports,
Год журнала:
2024,
Номер
14(1)
Опубликована: Май 14, 2024
The
length
of
3'
untranslated
regions
(3'UTR)
is
highly
regulated
during
many
transitions
in
cell
state,
including
T
activation,
through
the
process
alternative
polyadenylation
(APA).
However,
regulatory
mechanisms
and
functional
consequences
APA
remain
largely
unexplored.
Here
we
present
a
detailed
analysis
temporal
condition-specific
regulation
following
activation
primary
human
CD4+
cells.
We
find
that
global
changes
are
temporally
CD28
costimulatory
signals
enhance
subset
these
changes.
Most
upon
involve
3'UTR
shortening,
although
set
genes
enriched
for
function
mTOR
pathway
exhibit
lengthening.
While
upregulation
core
machinery
likely
induces
shortening
prolonged
stimulation;
significant
program
occur
prior
to
cellular
proliferation
or
machinery.
Motif
suggests
at
least
early
driven
by
RBM3,
an
RNA-binding
protein
which
competes
with
binding.
Together
this
work
expands
our
understanding
impact
response
new
may
be
regulated.
Vaccines,
Год журнала:
2024,
Номер
12(8), С. 873 - 873
Опубликована: Авг. 1, 2024
mRNA
vaccines
are
leading
a
medical
revolution.
technologies
utilize
the
host's
own
cells
as
bio-factories
to
produce
proteins
that
serve
antigens.
This
revolutionary
approach
circumvents
complicated
processes
involved
in
traditional
vaccine
production
and
empowers
with
ability
respond
emerging
or
mutated
infectious
diseases
rapidly.
Additionally,
robust
cellular
immune
response
elicited
by
has
shown
significant
promise
cancer
treatment.
However,
inherent
instability
of
complexity
tumor
immunity
have
limited
its
broader
application.
Although
emergence
pseudouridine
ionizable
cationic
lipid
nanoparticles
(LNPs)
made
clinical
application
possible,
there
remains
substantial
potential
for
further
improvement
immunogenicity
delivered
antigens
preventive
therapeutic
effects
technology.
Here,
we
review
latest
advancements
vaccines,
including
but
not
target
selection
delivery
systems.
offers
multifaceted
perspective
on
this
rapidly
evolving
field.
Nature Communications,
Год журнала:
2024,
Номер
15(1)
Опубликована: Май 14, 2024
Abstract
Although
more
than
half
of
all
genes
generate
transcripts
that
differ
in
3′UTR
length,
current
analysis
pipelines
only
quantify
the
amount
but
not
length
mRNA
transcripts.
is
determined
by
3′
end
cleavage
sites
(CS).
We
map
CS
200
primary
human
and
mouse
cell
types
increase
annotations
relative
to
GENCODE
database
40%.
Approximately
are
used
few
types,
revealing
most
have
one
or
two
major
ends.
incorporate
into
a
computational
pipeline,
called
scUTRquant,
for
rapid,
accurate,
simultaneous
quantification
gene
isoform
expression
from
single-cell
RNA
sequencing
(scRNA-seq)
data.
When
applying
scUTRquant
data
474
2134
perturbations,
we
discover
extensive
changes
across
as
widespread
coordinately
regulated
affect
mostly
different
genes.
Our
indicate
abundance
largely
independent
axes
regulation
together
determine
spatial
organization
protein
synthesis.
Cell Reports,
Год журнала:
2025,
Номер
44(2), С. 115237 - 115237
Опубликована: Фев. 1, 2025
The
subcellular
localization
of
mRNAs
plays
a
pivotal
role
in
biological
processes,
including
cell
migration.
For
instance,
β-actin
mRNA
and
its
associated
RNA-binding
protein
(RBP),
ZBP1/IGF2BP1,
are
recruited
to
focal
adhesions
(FAs)
support
localized
synthesis,
crucial
for
However,
whether
other
RBPs
also
localize
at
FAs
remains
unclear.
Here,
we
identify
hundreds
that
enriched
(FA-mRNAs).
FA-mRNAs
share
characteristics
with
stress
granule
(SG)
found
ribonucleoprotein
(RNP)
complexes
the
SG
RBP.
Mechanistically,
G3BP1
binds
FA
proteins
an
RNA-dependent
manner,
dimerization
domains,
essential
form
RNPs
SG,
required
We
find
promote
speed
by
enhancing
mobility
size.
These
findings
suggest
previously
unappreciated
regulating
function
under
non-stress
conditions.
bioRxiv (Cold Spring Harbor Laboratory),
Год журнала:
2024,
Номер
unknown
Опубликована: Фев. 2, 2024
SUMMARY
UPF1-mediated
decay
entails
several
mRNA
surveillance
pathways
that
play
a
crucial
role
in
cellular
homeostasis.
However,
the
precise
of
UPF1
postmitotic
neurons
remains
unresolved,
as
does
its
activity
amyotrophic
lateral
sclerosis
(ALS),
devastating
neurodegenerative
disease
characterized
by
TDP-43
pathology
and
disrupted
metabolism.
Here,
we
used
human
iPSC-derived
spinal
motor
(MNs)
to
identify
mRNAs
subject
degradation
integrating
RNA-seq
before
after
knockdown
with
RIP-seq
RNAs
co-immunoprecipitate
active
form
phosphorylated
UPF1.
We
define
stringent
set
bona
fide
targets
MNs
are
functionally
enriched
for
autophagy
structurally
GC-rich
long
3’
UTRs
but
not
premature
termination
codon
(PTC)-containing
transcripts.
depletion
reduces
phosphorylation
consequently
post-transcriptional
upregulation
targets,
suggesting
dysfunction
compromises
surveillance.
Intriguingly,
our
datasets
reveal
regulate
alternative
polyadenylation
3’UTR
length
associated
synaptic
axonal
function,
process
find
be
compromised
ALS
models
vitro
patient
tissue.
Our
study
provides
comprehensive
description
neurons,
reveals
overlapping
roles
between
regulating
length,
offers
novel
insight
into
intricate
interplay
RNA
metabolism
neurodegeneration
ALS.
Current Opinion in Cell Biology,
Год журнала:
2024,
Номер
88, С. 102357 - 102357
Опубликована: Апрель 15, 2024
In
the
past
decade,
a
growing
amount
of
evidence
has
demonstrated
that
organelles
do
not
act
autonomously
and
independently
but
rather
communicate
with
each
other
to
coordinate
different
processes
for
proper
cellular
function.
With
highly
extended
network
throughout
cell,
endoplasmic
reticulum
(ER)
plays
central
role
in
interorganelle
communication
through
membrane
contact
sites.
Here,
we
highlight
recent
indicating
ER
also
forms
contacts
membrane-less
organelles.
These
interactions
contribute
dynamic
assembly
disassembly
condensates
controlled
protein
secretion.
Additionally,
emerging
suggests
their
involvement
mRNA
localization
localized
translation.
We
further
explore
exciting
future
directions
this
theme
organelle
site
field.
