---
_id: '50149'
abstract:
- lang: eng
text: "Abstract\r\n RNA editing processes
are strikingly different in animals and plants. Up to thousands of specific cytidines
are converted into uridines in plant chloroplasts and mitochondria whereas up
to millions of adenosines are converted into inosines in animal nucleo-cytosolic
RNAs. It is unknown whether these two different RNA editing machineries are mutually
incompatible. RNA-binding pentatricopeptide repeat (PPR) proteins are the key
factors of plant organelle cytidine-to-uridine RNA editing. The complete absence
of PPR mediated editing of cytosolic RNAs might be due to a yet unknown barrier
that prevents its activity in the cytosol. Here, we transferred two plant mitochondrial
PPR-type editing factors into human cell lines to explore whether they could operate
in the nucleo-cytosolic environment. PPR56 and PPR65 not only faithfully edited
their native, co-transcribed targets but also different sets of off-targets in
the human background transcriptome. More than 900 of such off-targets with editing
efficiencies up to 91%, largely explained by known PPR-RNA binding properties,
were identified for PPR56. Engineering two crucial amino acid positions in its
PPR array led to predictable shifts in target recognition. We conclude that plant
PPR editing factors can operate in the entirely different genetic environment
of the human nucleo-cytosol and can be intentionally re-engineered towards new
targets."
author:
- first_name: Elena
full_name: Lesch, Elena
last_name: Lesch
- first_name: Maximilian T
full_name: Schilling, Maximilian T
last_name: Schilling
- first_name: Sarah
full_name: Brenner, Sarah
last_name: Brenner
- first_name: Yingying
full_name: Yang, Yingying
last_name: Yang
- first_name: Oliver J
full_name: Gruss, Oliver J
last_name: Gruss
- first_name: Volker
full_name: Knoop, Volker
last_name: Knoop
- first_name: Mareike
full_name: Schallenberg-Rüdinger, Mareike
last_name: Schallenberg-Rüdinger
citation:
ama: Lesch E, Schilling MT, Brenner S, et al. Plant mitochondrial RNA editing factors
can perform targeted C-to-U editing of nuclear transcripts in human cells. Nucleic
Acids Research. 2022;50(17):9966-9983. doi:10.1093/nar/gkac752
apa: Lesch, E., Schilling, M. T., Brenner, S., Yang, Y., Gruss, O. J., Knoop, V.,
& Schallenberg-Rüdinger, M. (2022). Plant mitochondrial RNA editing factors
can perform targeted C-to-U editing of nuclear transcripts in human cells. Nucleic
Acids Research, 50(17), 9966–9983. https://doi.org/10.1093/nar/gkac752
bibtex: '@article{Lesch_Schilling_Brenner_Yang_Gruss_Knoop_Schallenberg-Rüdinger_2022,
title={Plant mitochondrial RNA editing factors can perform targeted C-to-U editing
of nuclear transcripts in human cells}, volume={50}, DOI={10.1093/nar/gkac752},
number={17}, journal={Nucleic Acids Research}, publisher={Oxford University Press
(OUP)}, author={Lesch, Elena and Schilling, Maximilian T and Brenner, Sarah and
Yang, Yingying and Gruss, Oliver J and Knoop, Volker and Schallenberg-Rüdinger,
Mareike}, year={2022}, pages={9966–9983} }'
chicago: 'Lesch, Elena, Maximilian T Schilling, Sarah Brenner, Yingying Yang, Oliver J
Gruss, Volker Knoop, and Mareike Schallenberg-Rüdinger. “Plant Mitochondrial RNA
Editing Factors Can Perform Targeted C-to-U Editing of Nuclear Transcripts in
Human Cells.” Nucleic Acids Research 50, no. 17 (2022): 9966–83. https://doi.org/10.1093/nar/gkac752.'
ieee: 'E. Lesch et al., “Plant mitochondrial RNA editing factors can perform
targeted C-to-U editing of nuclear transcripts in human cells,” Nucleic Acids
Research, vol. 50, no. 17, pp. 9966–9983, 2022, doi: 10.1093/nar/gkac752.'
mla: Lesch, Elena, et al. “Plant Mitochondrial RNA Editing Factors Can Perform Targeted
C-to-U Editing of Nuclear Transcripts in Human Cells.” Nucleic Acids Research,
vol. 50, no. 17, Oxford University Press (OUP), 2022, pp. 9966–83, doi:10.1093/nar/gkac752.
short: E. Lesch, M.T. Schilling, S. Brenner, Y. Yang, O.J. Gruss, V. Knoop, M. Schallenberg-Rüdinger,
Nucleic Acids Research 50 (2022) 9966–9983.
date_created: 2024-01-04T08:23:01Z
date_updated: 2024-01-04T08:23:13Z
department:
- _id: '27'
doi: 10.1093/nar/gkac752
intvolume: ' 50'
issue: '17'
keyword:
- Genetics
language:
- iso: eng
page: 9966-9983
project:
- _id: '52'
name: 'PC2: Computing Resources Provided by the Paderborn Center for Parallel Computing'
publication: Nucleic Acids Research
publication_identifier:
issn:
- 0305-1048
- 1362-4962
publication_status: published
publisher: Oxford University Press (OUP)
status: public
title: Plant mitochondrial RNA editing factors can perform targeted C-to-U editing
of nuclear transcripts in human cells
type: journal_article
user_id: '67287'
volume: 50
year: '2022'
...
---
_id: '22637'
abstract:
- lang: eng
text: "Abstract\r\n Doxorubicin (DOX)
is a common drug in cancer chemotherapy, and its high DNA-binding affinity can
be harnessed in preparing DOX-loaded DNA nanostructures for targeted delivery
and therapeutics. Although DOX has been widely studied, the existing literature
of DOX-loaded DNA-carriers remains limited and incoherent. Here, based on an in-depth
spectroscopic analysis, we characterize and optimize the DOX loading into different
2D and 3D scaffolded DNA origami nanostructures (DONs). In our experimental conditions,
all DONs show similar DOX binding capacities (one DOX molecule per two to three
base pairs), and the binding equilibrium is reached within seconds, remarkably
faster than previously acknowledged. To characterize drug release profiles, DON
degradation and DOX release from the complexes upon DNase I digestion was studied.
For the employed DONs, the relative doses (DOX molecules released per unit time)
may vary by two orders of magnitude depending on the DON superstructure. In addition,
we identify DOX aggregation mechanisms and spectral changes linked to pH, magnesium,
and DOX concentration. These features have been largely ignored in experimenting
with DNA nanostructures, but are probably the major sources of the incoherence
of the experimental results so far. Therefore, we believe this work can act as
a guide to tailoring the release profiles and developing better drug delivery
systems based on DNA-carriers."
author:
- first_name: Heini
full_name: Ijäs, Heini
last_name: Ijäs
- first_name: Boxuan
full_name: Shen, Boxuan
last_name: Shen
- first_name: Amelie
full_name: Heuer-Jungemann, Amelie
last_name: Heuer-Jungemann
- first_name: Adrian
full_name: Keller, Adrian
id: '48864'
last_name: Keller
orcid: 0000-0001-7139-3110
- first_name: Mauri A
full_name: Kostiainen, Mauri A
last_name: Kostiainen
- first_name: Tim
full_name: Liedl, Tim
last_name: Liedl
- first_name: Janne A
full_name: Ihalainen, Janne A
last_name: Ihalainen
- first_name: Veikko
full_name: Linko, Veikko
last_name: Linko
citation:
ama: Ijäs H, Shen B, Heuer-Jungemann A, et al. Unraveling the interaction between
doxorubicin and DNA origami nanostructures for customizable chemotherapeutic drug
release. Nucleic Acids Research. 2021;49:3048-3062. doi:10.1093/nar/gkab097
apa: Ijäs, H., Shen, B., Heuer-Jungemann, A., Keller, A., Kostiainen, M. A., Liedl,
T., … Linko, V. (2021). Unraveling the interaction between doxorubicin and DNA
origami nanostructures for customizable chemotherapeutic drug release. Nucleic
Acids Research, 49, 3048–3062. https://doi.org/10.1093/nar/gkab097
bibtex: '@article{Ijäs_Shen_Heuer-Jungemann_Keller_Kostiainen_Liedl_Ihalainen_Linko_2021,
title={Unraveling the interaction between doxorubicin and DNA origami nanostructures
for customizable chemotherapeutic drug release}, volume={49}, DOI={10.1093/nar/gkab097},
journal={Nucleic Acids Research}, author={Ijäs, Heini and Shen, Boxuan and Heuer-Jungemann,
Amelie and Keller, Adrian and Kostiainen, Mauri A and Liedl, Tim and Ihalainen,
Janne A and Linko, Veikko}, year={2021}, pages={3048–3062} }'
chicago: 'Ijäs, Heini, Boxuan Shen, Amelie Heuer-Jungemann, Adrian Keller, Mauri A
Kostiainen, Tim Liedl, Janne A Ihalainen, and Veikko Linko. “Unraveling the Interaction
between Doxorubicin and DNA Origami Nanostructures for Customizable Chemotherapeutic
Drug Release.” Nucleic Acids Research 49 (2021): 3048–62. https://doi.org/10.1093/nar/gkab097.'
ieee: H. Ijäs et al., “Unraveling the interaction between doxorubicin and
DNA origami nanostructures for customizable chemotherapeutic drug release,” Nucleic
Acids Research, vol. 49, pp. 3048–3062, 2021.
mla: Ijäs, Heini, et al. “Unraveling the Interaction between Doxorubicin and DNA
Origami Nanostructures for Customizable Chemotherapeutic Drug Release.” Nucleic
Acids Research, vol. 49, 2021, pp. 3048–62, doi:10.1093/nar/gkab097.
short: H. Ijäs, B. Shen, A. Heuer-Jungemann, A. Keller, M.A. Kostiainen, T. Liedl,
J.A. Ihalainen, V. Linko, Nucleic Acids Research 49 (2021) 3048–3062.
date_created: 2021-07-08T11:46:53Z
date_updated: 2022-01-06T06:55:37Z
department:
- _id: '302'
doi: 10.1093/nar/gkab097
intvolume: ' 49'
language:
- iso: eng
page: 3048-3062
publication: Nucleic Acids Research
publication_identifier:
issn:
- 0305-1048
- 1362-4962
publication_status: published
status: public
title: Unraveling the interaction between doxorubicin and DNA origami nanostructures
for customizable chemotherapeutic drug release
type: journal_article
user_id: '48864'
volume: 49
year: '2021'
...