Rare Diseases Symptoms Automatic Extraction
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A random Abstract
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Translational control of SEPT9 isoforms is perturbed in disease.
[neuralgic amyotrophy]
A
common
feature
of
the
mammalian
septin
gene
family
is
complex
genomic
architecture
with
multiple
alternate
splice
variants
.
Septin
9
has
18
distinct
transcripts
encoding
15
polypeptides
,
with
two
transcripts
(
SEPT
9
_
v
4
and
v
4
*
)
encoding
the
same
polypeptide
.
We
have
previously
reported
that
the
ratio
of
these
distinct
transcripts
is
altered
in
neoplasia
,
with
the
v
4
transcript
being
the
usual
form
in
normal
cells
but
v
4
*
becoming
predominant
in
tumours
.
This
led
us
to
ask
what
the
functional
differences
between
these
two
transcripts
might
be
.
The
5
'
-
UTRs
of
v
4
and
v
4
*
have
distinct
5
'
ends
encoded
by
exons
1
beta
(
v
4
)
and
1
zeta
and
2
(
v
4
*
)
and
a
common
3
'
region
and
initiating
ATG
encoded
within
exon
3
.
Here
we
show
that
the
two
mRNAs
are
translated
with
different
efficiencies
and
that
cellular
stress
can
alter
this
.
A
putative
internal
ribosome
entry
site
can
be
identified
in
the
common
region
of
the
v
4
and
v
4
*
5
'
-
UTRs
and
translation
is
modulated
by
an
upstream
open
-reading
frame
in
the
unique
region
of
the
v
4
5
'
-
UTR
.
Germline
mutations
in
hereditary
neuralgic
amyotrophy
(
HNA
)
map
to
the
region
which
is
common
to
the
two
UTRs
.
These
mutations
dramatically
enhance
the
translational
efficiency
of
the
v
4
5
'
-
UTR
,
leading
to
elevated
SEPT
9
_
v
4
protein
under
hypoxic
conditions
.
Our
data
provide
a
mechanistic
insight
into
how
the
HNA
mutations
can
alter
the
fine
control
of
SEPT
9
_
v
4
protein
and
its
regulation
under
physiologically
relevant
conditions
and
are
consistent
with
the
episodic
and
stress-induced
nature
of
the
clinical
features
of
HNA
.
