bioRxiv (Cold Spring Harbor Laboratory),
Год журнала:
2024,
Номер
unknown
Опубликована: Дек. 11, 2024
Abstract
PRMT1
is
the
predominant
type
I
protein
arginine
methyltransferase
responsible
for
generating
monomethylarginine
and
asymmetric
dimethylarginine
(MMA
ADMA)
in
various
substrates.
It
regulates
numerous
biological
processes,
including
RNA
metabolism,
mRNA
splicing,
DNA
damage
repair,
chromatin
dynamics.
The
crystal
structure
of
rat
has
been
previously
reported
as
a
homodimer;
however,
higher-order
oligomeric
species
human
have
observed
vivo,
their
structural
basis
remains
elusive.
In
this
study,
we
present
cryo-EM
its
form,
revealing
novel
interfaces
crucial
self-assembly
normal
function.
shows
strong
preference
intrinsically
disordered
RGG/RG
motifs,
which
are
commonly
found
RNA-binding
proteins
(RBPs),
highlighting
critical
role
regulating
metabolism.
vitro
studies
indicate
that
disrupting
oligomerization
impairs
binding
affinity
RGG
motif
substrates,
thereby
reducing
methylation
levels
on
these
This
finding
emphasizes
essential
state
function
with
motif-containing
RBPs.
loss
leads
to
decreased
global
ADMA
pancreatic
ductal
adenocarcinoma
(PDAC)
cells
inhibits
PDAC
tumor
growth.
Collectively,
propose
oligomerization,
rather
than
mere
dimerization,
sufficient
PRMT1-driven
growth,
offering
insights
into
potential
therapeutic
targeting
forms
PDAC.
Graphical
abstract
Frontiers in Immunology,
Год журнала:
2024,
Номер
15
Опубликована: Ноя. 15, 2024
Histones
play
crucial
roles
in
both
promoting
and
repressing
gene
expression,
primarily
regulated
through
post-translational
modifications
(PTMs)
at
specific
amino
acid
residues.
Histone
PTMs,
including
methylation,
acetylation,
ubiquitination,
phosphorylation,
lactylation,
butyrylation,
propionylation,
act
as
important
epigenetic
markers.
These
influence
not
only
chromatin
compaction
but
also
expression.
Their
importance
extends
to
the
treatment
prevention
of
various
human
diseases,
particularly
cancer,
due
their
involvement
key
cellular
processes.
Abnormal
histone
enzymes
responsible
for
these
alterations
often
serve
critical
drivers
tumor
cell
proliferation,
invasion,
apoptosis,
stemness.
This
review
introduces
PTMs
modifications,
examining
impact
on
tumorigenesis
cancer
progression.
Furthermore,
it
explores
therapeutic
strategies
targeting
offers
recommendations
identifying
new
potential
targets.
bioRxiv (Cold Spring Harbor Laboratory),
Год журнала:
2024,
Номер
unknown
Опубликована: Дек. 11, 2024
Abstract
PRMT1
is
the
predominant
type
I
protein
arginine
methyltransferase
responsible
for
generating
monomethylarginine
and
asymmetric
dimethylarginine
(MMA
ADMA)
in
various
substrates.
It
regulates
numerous
biological
processes,
including
RNA
metabolism,
mRNA
splicing,
DNA
damage
repair,
chromatin
dynamics.
The
crystal
structure
of
rat
has
been
previously
reported
as
a
homodimer;
however,
higher-order
oligomeric
species
human
have
observed
vivo,
their
structural
basis
remains
elusive.
In
this
study,
we
present
cryo-EM
its
form,
revealing
novel
interfaces
crucial
self-assembly
normal
function.
shows
strong
preference
intrinsically
disordered
RGG/RG
motifs,
which
are
commonly
found
RNA-binding
proteins
(RBPs),
highlighting
critical
role
regulating
metabolism.
vitro
studies
indicate
that
disrupting
oligomerization
impairs
binding
affinity
RGG
motif
substrates,
thereby
reducing
methylation
levels
on
these
This
finding
emphasizes
essential
state
function
with
motif-containing
RBPs.
loss
leads
to
decreased
global
ADMA
pancreatic
ductal
adenocarcinoma
(PDAC)
cells
inhibits
PDAC
tumor
growth.
Collectively,
propose
oligomerization,
rather
than
mere
dimerization,
sufficient
PRMT1-driven
growth,
offering
insights
into
potential
therapeutic
targeting
forms
PDAC.
Graphical
abstract
