Science Advances,
Journal Year:
2024,
Volume and Issue:
10(46)
Published: Nov. 13, 2024
Translation-targeting
toxic
small
alarmone
synthetases
(toxSAS)
are
effectors
of
bacterial
toxin-antitoxin
systems
that
pyrophosphorylate
the
3′-CCA
end
transfer
RNA
(tRNA)
to
prevent
aminoacylation.
toxSAS
implicated
in
antiphage
immunity:
Phage
detection
triggers
activity
shut
down
viral
production.
We
show
FaRel2
inspects
tRNA
acceptor
stem
specifically
select
Gly
and
Thr
.
The
first,
second,
fourth,
fifth
base
pairs
act
as
specificity
determinants.
toxSASs
PhRel2
CapRel
SJ46
differ
from
rationalize
this
through
structural
modeling:
While
universal
slots
into
a
highly
conserved
CCA
recognition
groove,
region
is
variable
across
diversity.
As
phages
use
isoacceptors
overcome
tRNA-targeting
defenses,
we
hypothesize
evolvable
modular
allows
for
escape
countermeasures
substrate
switching.
bioRxiv (Cold Spring Harbor Laboratory),
Journal Year:
2025,
Volume and Issue:
unknown
Published: May 10, 2025
Abstract
Double-stranded
(ds)
RNAs
are
major
structural
components
of
the
transcriptome,
hallmarks
viral
infection,
and
primary
triggers
innate
immune
responses.
The
J2
monoclonal
antibody
is
gold-standard
method
to
discover
map
endogenous
dsRNAs
across
subcellular
locations
cell
surfaces,
detect
exogenous
in
surveil
mRNA
prophylactics
therapeutics
for
inflammatory
dsRNAs.
To
define
its
epitope,
specificity,
mechanism,
we
determine
a
2.85
Å
co-crystal
structure
antigen-binding
fragment
(Fab)
bound
dsRNA.
uses
heavy
light
chains
tandem
track
dsRNA
minor
groove,
recognizing
staggered
8-bp
duplex.
exquisitely
selective
dsRNAs,
requires
14
bp
robust
binding,
exhibits
greatly
diminished
binding
GC-rich
R-loop-specific
S9.6
share
common
recognition
strategy
distinct
from
intracellular
dsRNA-binding
proteins.
This
study
provides
mechanistic
insights
into
establishes
framework
reliable
application
data
interpretation
RNA
discovery.
Nature Communications,
Journal Year:
2024,
Volume and Issue:
15(1)
Published: July 29, 2024
Abstract
The
widespread
oligonucleotide/oligosaccharide-binding
(OB)-fold
recognizes
diverse
substrates
from
sugars
to
nucleic
acids
and
proteins,
plays
key
roles
in
genome
maintenance,
transcription,
translation,
tRNA
metabolism.
OB-containing
bacterial
Trbp
yeast
Arc1p
proteins
are
thought
recognize
the
elbow
or
anticodon
regions.
Here
we
report
a
2.6
Å
co-crystal
structure
of
Aquifex
aeolicus
Trbp111
bound
Ile
,
which
reveals
that
tRNAs
solely
by
capturing
their
3′
ends.
Structural,
mutational,
biophysical
analyses
show
Trbp/EMAPII-like
OB
fold
precisely
single-stranded
structure,
terminal
location,
specific
sequence
CA
dinucleotide
—
universal
feature
mature
tRNAs.
supplements
its
–
end
interaction
with
additional
contacts
involve
an
adjacent
basic
region
body.
This
study
uncovers
previously
unrecognized
mode
recognition
ancient
protein
fold,
provides
insights
into
protein-mediated
aminoacylation,
folding,
localization,
trafficking,
piracy.
Cell Death Discovery,
Journal Year:
2024,
Volume and Issue:
10(1)
Published: July 17, 2024
Abstract
tRNA
is
the
RNA
type
that
undergoes
most
modifications
among
known
RNA,
and
in
recent
years,
methylation
has
emerged
as
a
crucial
process
regulating
gene
translation.
Dysregulation
of
abundance
occurs
cancer
cells,
along
with
increased
expression
activity
methyltransferases
to
raise
level
modification
stability.
This
leads
hijacking
translation
synthesis
multiple
proteins
associated
tumor
proliferation,
metastasis,
invasion,
autophagy,
chemotherapy
resistance,
metabolic
reprogramming.
In
this
review,
we
provide
an
overview
current
research
on
clarify
its
involvement
human
malignancies
establish
theoretical
framework
for
future
therapeutic
interventions
targeting
processes.
Journal of Biological Chemistry,
Journal Year:
2024,
Volume and Issue:
300(9), P. 107679 - 107679
Published: Aug. 16, 2024
Transfer
RNAs
(tRNA)
are
essential
small
non-coding
that
enable
the
translation
of
genomic
information
into
proteins
in
all
life
forms.
The
principal
function
tRNAs
is
to
bring
amino
acid
building
blocks
ribosomes
for
protein
synthesis.
In
ribosome,
interact
with
messenger
RNA
(mRNA)
mediate
incorporation
acids
a
growing
polypeptide
chain
following
rules
genetic
code.
Accurate
interpretation
code
requires
carry
matching
their
anticodon
identity
and
decode
correct
codon
on
mRNAs.
Errors
these
steps
cause
codons
wrong
(mistranslation),
compromising
accurate
flow
from
DNA
proteins.
Accumulation
mutant
due
mistranslation
jeopardizes
proteostasis
cellular
viability.
However,
concept
evolving,
increasing
evidence
indicating
can
be
used
as
mechanism
survival
acclimatization
environmental
conditions.
this
review,
we
discuss
central
role
modulating
translational
fidelity
through
dynamic
complex
interplay
factors.
We
summarize
recent
discoveries
mistranslating
describe
underlying
molecular
mechanisms
specific
conditions
environments
promote
mistranslation.
bioRxiv (Cold Spring Harbor Laboratory),
Journal Year:
2024,
Volume and Issue:
unknown
Published: July 6, 2024
Abstract
Translation-targeting
toxic
Small
Alarmone
Synthetases
(toxSAS)
are
effectors
of
bacterial
Toxin-Antitoxin
systems
that
pyrophosphorylate
the
3’-CCA
end
tRNA
to
prevent
aminoacylation.
toxSAS
implicated
in
antiphage
immunity:
phage
detection
triggers
activity
shut
down
viral
production.
We
show
FaRel2
inspects
acceptor
stem
specifically
select
Gly
and
Thr
.
The
1
st
,
2
nd
4
th
5
base
pairs
act
as
specificity
determinants.
toxSASs
PhRel2
CapRel
SJ46
differ
from
FaRel2,
rationalise
this
through
structural
modelling:
while
universal
slots
into
a
highly
conserved
CCA
recognition
groove,
region
is
variable
across
diversity.
As
phages
use
isoacceptors
overcome
tRNA-targeting
defences,
we
hypothesise
evolvable
modular
allows
for
escape
countermeasures
substrate
switching.
