Science,
Год журнала:
2024,
Номер
386(6721), С. 551 - 560
Опубликована: Окт. 31, 2024
The
spliceosome
is
the
complex
molecular
machinery
that
sequentially
assembles
on
eukaryotic
messenger
RNA
precursors
to
remove
introns
(pre-mRNA
splicing),
a
physiologically
regulated
process
altered
in
numerous
pathologies.
We
report
transcriptome-wide
analyses
upon
systematic
knock
down
of
305
components
and
regulators
human
cancer
cells
reconstruction
functional
splicing
factor
networks
govern
different
classes
alternative
decisions.
results
disentangle
intricate
circuits
cross-regulation,
reveal
precise
architecture
late-assembling
U4/U6.U5
tri-small
nuclear
ribonucleoprotein
(snRNP)
complexes
regulates
splice
site
pairing,
discover
an
unprecedented
division
labor
among
protein
U1
snRNP
for
regulating
exon
definition
5'
selection.
Thus,
we
provide
resource
explore
physiological
pathological
mechanisms
regulation.
Signaling
from
pathogen
sensing
to
effector
activation
is
a
fundamental
principle
of
cellular
immunity.
While
cyclic
(oligo)nucleotides
have
emerged
as
key
signaling
molecules,
the
existence
other
messengers
remains
largely
unexplored.
Here,
we
reveal
bacterial
anti-phage
system
that
mediates
immune
through
nucleobase
modification.
Immunity
triggered
by
phage
nucleotide
kinases,
which,
combined
with
system-encoded
adenosine
deaminase,
produce
deoxyinosine
5′-triphosphate
(dITP)
messengers.
The
dITP
signal
activates
downstream
mediate
NAD
+
depletion,
resulting
in
population-level
defense
death
infected
cells.
To
counteract
signaling,
phages
deploy
specialized
enzymes
deplete
dAMP,
precursor
Our
findings
uncover
modification-based
pathway,
establishing
noncanonical
nucleotides
new
type
bacteria.
Nature Cell Biology,
Год журнала:
2025,
Номер
unknown
Опубликована: Март 21, 2025
Abstract
Prohibitins
are
a
highly
conserved
family
of
proteins
that
have
been
implicated
in
variety
functions
including
mitochondrial
stress
signalling
and
housekeeping,
cell
cycle
progression,
apoptosis,
lifespan
regulation
many
others.
The
human
prohibitins
prohibitin
1
2
proposed
to
act
as
scaffolds
within
the
inner
membrane,
but
their
molecular
organization
has
remained
elusive.
Here
we
determined
complex
membrane
using
an
integrative
structural
biology
approach
combining
quantitative
western
blotting,
cryo-electron
tomography,
subtomogram
averaging
modelling.
bell-shaped
structure
consists
11
alternating
molecules.
This
study
reveals
average
about
43
complexes
per
crista,
covering
1–3%
crista
area.
These
findings
provide
basis
for
understanding
functional
contributions
integrity
spatial
membrane.
Nature Communications,
Год журнала:
2024,
Номер
15(1)
Опубликована: Май 17, 2024
Abstract
Bacteriophage
infection,
a
pivotal
process
in
microbiology,
initiates
with
the
phage’s
tail
recognizing
and
binding
to
bacterial
cell
surface,
which
then
mediates
injection
of
viral
DNA.
Although
comprehensive
studies
on
interaction
between
bacteriophage
lambda
its
outer
membrane
receptor,
LamB,
have
provided
rich
information
about
system’s
biochemical
properties,
precise
molecular
mechanism
remains
undetermined.
This
study
revealed
high-resolution
cryo-electron
microscopy
(cryo-EM)
structures
complexed
irreversible
Shigella
sonnei
3070
LamB
receptor
closed
central
fiber.
These
reveal
complex
processes
that
trigger
infection
demonstrate
substantial
conformational
change
phage
tip
upon
binding.
Providing
detailed
initiation,
this
contributes
expanding
knowledge
lambda-bacterial
interaction,
holds
significance
fields
microbiology
therapeutic
development.
Science,
Год журнала:
2024,
Номер
386(6721), С. 551 - 560
Опубликована: Окт. 31, 2024
The
spliceosome
is
the
complex
molecular
machinery
that
sequentially
assembles
on
eukaryotic
messenger
RNA
precursors
to
remove
introns
(pre-mRNA
splicing),
a
physiologically
regulated
process
altered
in
numerous
pathologies.
We
report
transcriptome-wide
analyses
upon
systematic
knock
down
of
305
components
and
regulators
human
cancer
cells
reconstruction
functional
splicing
factor
networks
govern
different
classes
alternative
decisions.
results
disentangle
intricate
circuits
cross-regulation,
reveal
precise
architecture
late-assembling
U4/U6.U5
tri-small
nuclear
ribonucleoprotein
(snRNP)
complexes
regulates
splice
site
pairing,
discover
an
unprecedented
division
labor
among
protein
U1
snRNP
for
regulating
exon
definition
5'
selection.
Thus,
we
provide
resource
explore
physiological
pathological
mechanisms
regulation.
