The RNA binding proteins LARP4A and LARP4B promote sarcoma and carcinoma growth and metastasis
iScience,
Год журнала:
2024,
Номер
27(4), С. 109288 - 109288
Опубликована: Фев. 24, 2024
Язык: Английский
The short conserved region-2 of LARP4 interacts with ribosome-associated RACK1 and promotes translation
Nucleic Acids Research,
Год журнала:
2025,
Номер
53(3)
Опубликована: Янв. 24, 2025
LARP4
interacts
with
poly(A)-binding
protein
(PABP)
to
protect
messenger
RNAs
(mRNAs)
from
deadenylation
and
decay,
recent
data
indicate
it
can
direct
the
translation
of
functionally
related
mRNA
subsets.
was
known
bind
RACK1,
a
ribosome-associated
protein,
although
specific
regions
involved
relevance
had
been
undetermined.
Here,
through
combination
in-cell
in
vitro
methodologies,
we
identified
positions
615-625
conserved
region-2
(CR2)
(and
646-656
LARP4B)
as
directly
binding
RACK1.
Consistent
these
results,
AlphaFold2-Multimer
predicted
high-confidence
interaction
CR2
RACK1
propellers
5
6.
mutations
strongly
decreased
association
cellular
ribosomes
by
multiple
assays,
whereas
PABP
less
affected,
consistent
independent
interactions.
The
LARP4's
ability
stabilize
β-globin
reporter
containing
an
AU-rich
element
(ARE)
higher
degree
than
GFP
(green
fluorescent
protein)
mRNAs
lacking
ARE.
We
show
robustly
increases
β-glo-ARE
mRNA,
mutant
is
impaired.
Analysis
nanoLuc-ARE
for
production
luciferase
activity
confirmed
promotes
efficiency,
while
are
disabling.
Thus,
CR2-mediated
promote
translational
efficiency
some
mRNAs.
Язык: Английский
1H, 13C, and 15N resonance assignment of the 5’SL-bound La domain of the human La-related protein 6
Biomolecular NMR Assignments,
Год журнала:
2025,
Номер
unknown
Опубликована: Апрель 30, 2025
Язык: Английский
LARP4 is an RNA-binding protein that binds nuclear-encoded mitochondrial mRNAs to promote mitochondrial function
RNA,
Год журнала:
2023,
Номер
30(3), С. 223 - 239
Опубликована: Дек. 20, 2023
Mitochondria-associated
RNA-binding
proteins
(RBPs)
have
emerged
as
key
contributors
to
mitochondrial
biogenesis
and
homeostasis.
With
few
examples
known,
we
set
out
identify
RBPs
that
regulate
nuclear-encoded
mRNAs
(NEMmRNAs).
Our
systematic
analysis
of
RNA
targets
150
identified
with
a
preference
for
binding
NEMmRNAs,
including
LARP4,
La
RBP
family
member.
We
show
LARP4's
are
particularly
enriched
in
encode
respiratory
chain
complex
(RCCPs)
ribosome
(MRPs)
across
multiple
human
cell
lines.
Through
quantitative
proteomics,
demonstrate
depletion
LARP4
leads
significant
reduction
RCCP
MRP
protein
levels.
Furthermore,
reduces
function,
re-expression
rescues
this
phenotype.
findings
shed
light
on
novel
function
an
binds
positively
regulates
NEMmRNAs
promote
function.
Язык: Английский
The short conserved region-2 of LARP4 interacts with ribosome-associated RACK1 and promotes translation
bioRxiv (Cold Spring Harbor Laboratory),
Год журнала:
2024,
Номер
unknown
Опубликована: Ноя. 1, 2024
ABSTRACT
LARP4
interacts
with
poly(A)-binding
protein
(PABP)
to
protect
mRNAs
from
deadenylation
and
decay,
recent
data
indicate
it
can
direct
the
translation
of
functionally
related
mRNA
subsets.
was
known
bind
RACK1,
a
ribosome-associated
protein,
although
specific
regions
involved,
relevance
had
been
undetermined.
Here,
yeast
two-hybrid
domain
mapping
followed
by
other
methods
identified
positions
615-625
in
conserved
region-2
(CR2)
(and
LARP4B)
as
directly
binding
RACK1
region
200-317.
Consistent
these
results,
AlphaFold2-multimer
predicted
high
confidence
interaction
CR2
propellers
5-6.
mutations
strongly
decreased
association
cellular
ribosomes
multiple
assays,
whereas
less
effect
observed
for
PABP
association,
consistent
independent
interactions.
ability
optimally
stabilize
β-globin
reporter
containing
an
AU-rich
element
(ARE)
more
significantly
than
reporters
lacking
this
element.
While
polysome
profiles
β-glo-ARE
is
inefficiently
translated,
published
data,
we
show
that
increases
its
LARP4-CR2
mutant
impaired.
Analysis
nanoLuc-ARE
production
luciferase
activity
confirmed
promotes
efficiency
while
are
disabling.
Thus,
CR2-mediated
promote
translational
some
mRNAs.
Язык: Английский
Overexpression of lncRNA LINC00294 Induces Cell Cycle Arrest and Apoptosis in Colorectal Cancer by Regulating the miR‐499a‐5p/LARP4B Axis
Journal of Biochemical and Molecular Toxicology,
Год журнала:
2024,
Номер
39(1)
Опубликована: Дек. 24, 2024
Increasing
long
noncoding
RNAs
(lncRNAs)
have
been
found
to
participate
in
regulating
the
progression
of
colorectal
cancer
(CRC),
which
is
a
common
gastrointestinal
malignancy.
Here,
specific
role
and
mechanisms
lncRNA
LINC00294
were
investigated
CRC.
The
expression
levels
LINC00294,
miR-499a-5p,
La-related
protein
4B
(LARP4B)
CRC
cells
(HCT116
SW620)
tissues
assessed
by
RT-qPCR.
viability,
proliferation,
cell
cycle,
apoptosis
HCT116
SW620
determined
CCK-8,
EdU,
flow
cytometry
assays.
Protein
cycle
markers
measured
western
blot
analysis.
FISH
assay
was
performed
evaluate
subcellular
localization
cells.
Luciferase
reporter
assay,
RNA
pull-down
as
well
RIP
verified
interactions
between
miR-499a-5p
(or
LARP4B).
xenograft
model
established
mice
investigate
function
vivo.
presented
decreased
level
tissues.
overexpression
suppressed
proliferative
capacity,
promoted
arrest,
induced
interacted
with
targeted
LARP4B.
MiR-499a-5p
upregulated
while
LARP4B
downregulated
In
rescue
assays,
knockdown
reversed
inhibition
on
malignant
phenotypes
model,
inhibited
tumor
growth
exerted
an
antitumor
forming
LINC00294/miR-499a-5p/LARP4B
regulatory
network.
Язык: Английский