Single-molecule epitranscriptomic analysis of full-length HIV-1 RNAs reveals functional roles of site-specific m6As
Alice Baek,
No information about this author
Ga-Eun Lee,
No information about this author
Sarah Golconda
No information about this author
et al.
Nature Microbiology,
Journal Year:
2024,
Volume and Issue:
9(5), P. 1340 - 1355
Published: April 11, 2024
Abstract
Although
the
significance
of
chemical
modifications
on
RNA
is
acknowledged,
evolutionary
benefits
and
specific
roles
in
human
immunodeficiency
virus
(HIV-1)
replication
remain
elusive.
Most
studies
have
provided
only
population-averaged
values
for
fragmented
RNAs
at
low
resolution
relied
indirect
analyses
phenotypic
effects
by
perturbing
host
effectors.
Here
we
analysed
HIV-1
full-length,
single
level
nucleotide
using
direct
sequencing
methods.
Our
data
reveal
an
unexpectedly
simple
modification
landscape,
highlighting
three
predominant
N
6
-methyladenosine
(m
A)
near
3′
end.
More
densely
installed
spliced
viral
messenger
than
genomic
RNAs,
these
m
As
play
a
crucial
role
maintaining
normal
levels
splicing
translation.
generates
diverse
subspecies
with
distinct
A
ensembles,
multiple
its
provides
additional
stability
resilience
to
replication,
suggesting
unexplored
RNA-level
strategy.
Language: Английский
YTHDF1 and YTHDC1 m 6 A reader proteins regulate HTLV-1 tax and hbz activity
Emily M. King,
No information about this author
Amanda Midkiff,
No information about this author
Karsyn McClain
No information about this author
et al.
Journal of Virology,
Journal Year:
2025,
Volume and Issue:
unknown
Published: Feb. 4, 2025
ABSTRACT
Human
T-cell
leukemia
virus
type
1
(HTLV-1)
is
a
retrovirus
responsible
for
adult
leukemia/lymphoma
(ATLL)
and
HTLV-1-associated
myelopathy/tropical
spastic
paraparesis
(HAM/TSP),
progressive
neurodegenerative
disease.
Regulation
of
viral
gene
expression
plays
key
role
in
persistence
pathogenesis.
However,
the
molecular
mechanisms
underlying
this
fine-tuned
regulation
remain
poorly
understood.
Little
known
regarding
RNA
chemical
modifications
HTLV-1
how
these
affect
biology
disease
development.
Post-transcriptional
modification
common
eukaryotes,
with
N
6
-methyladenosine
(m
A)
being
most
prevalent.
In
study,
we
investigated
m
A
on
expression.
Using
MeRIP-Seq,
mapped
sites
to
3’
end
genome.
We
found
RNA,
as
well
oncogene
transcripts
tax
hbz
,
contained
modifications.
A-depletion
HTLV-1-transformed
cells
decreased
sense-derived
genes
(
Tax,
Gag,
Env
)
increased
antisense-derived
Hbz
Tax
were
bound
by
reader
proteins
YTHDF1
YTHDC1
panel
lines.
vectors
shRNA-mediated
knockdown,
that
had
opposing
effects
expression,
decreasing
increasing
.
Upon
further
abundance
dependent
deposition.
The
nuclear
protein
affected
both
sense-
specifically
enhanced
export
transcript.
Collectively,
our
results
demonstrate
global
levels
regulate
IMPORTANCE
pathogenesis
are
controlled
through
tight
fate
can
be
epigenetic
impact
without
altering
DNA
sequence.
Our
study
details
N6-methyladenosine
reductions
other
genes,
whereas
suggest
oncogenic
transcripts,
A-modified
cells.
interpreted
YTHDC1,
which
dictate
RNA.
Understanding
offers
potential
insights
into
novel
therapeutic
strategies
diseases.
Language: Английский
Resolving sequencing-based HIV-1 epitranscriptomics
Michael S. Bosmeny,
No information about this author
João I. Mamede,
No information about this author
Keith T. Gagnon
No information about this author
et al.
Epigenomics,
Journal Year:
2025,
Volume and Issue:
unknown, P. 1 - 12
Published: May 16, 2025
The
collection
of
HIV-1
RNA
chemical
modifications
and
their
functional
consequences
in
viral
gene
expression,
host
interactions,
the
life
cycle,
referred
to
as
epitranscriptomics,
remain
incompletely
understood.
While
field
is
evolving,
diverse
modification
discovery
methods,
cell
lines,
sequences,
bioinformatics
methods
make
a
consensus
view
epitranscriptome
difficult
resolve.
Here,
we
review
for
identifying
interpreting
N6-methyladenosine
(m6A),
5-methylcytosine
(m5C),
pseudouridine
(Ψ),
2´-O-methylation
(Nm),
N4-acetylcytidine
(ac4C)
HIV-1,
including
antibody-based
selection
chemical-treatment-based
detection
by
nanopore
direct
sequencing.
We
recommend
adoption
latter
standardized
sequencing
strategy
enable
better
benchmarking
across
studies
help
resolve
epitranscriptomics.
Language: Английский