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Science. 2019 Mar 29;363(6434). pii: eaaw2644. doi: 10.1126/science.aaw2644.

Designer membraneless organelles enable codon reassignment of selected mRNAs in eukaryotes.

Author information

1
Biocentre, Departments of Biology and Chemistry, Pharmacy and Geosciences, Johannes Gutenberg-University Mainz, Hanns-Dieter-Hüsch-Weg 15, 55128 Mainz, Germany.
2
Institute of Molecular Biology, Ackermannweg 4, 55128 Mainz, Germany.
3
Structural and Computational Biology Unit and Cell Biology and Biophysics Unit, European Molecular Biology Laboratory, Meyerhofstrasse 1, 69117 Heidelberg, Germany.
4
Biocentre, Departments of Biology and Chemistry, Pharmacy and Geosciences, Johannes Gutenberg-University Mainz, Hanns-Dieter-Hüsch-Weg 15, 55128 Mainz, Germany. edlemke@uni-mainz.de.
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Contributed equally

Abstract

Nature regulates interference between cellular processes-allowing more complexity of life-by confining specific functions to organelles. Inspired by this concept, we designed an artificial organelle dedicated to protein engineering. We generated a membraneless organelle to translate only one type of messenger RNA-by recruiting an RNA-targeting system, stop codon-suppression machinery, and ribosomes-by means of phase separation and spatial targeting. This enables site-specific protein engineering with a tailored noncanonical function in response to one specific codon in the entire genome only in the protein of choice. Our results demonstrate a simple yet effective approach to the generation of artificial organelles that provides a route toward customized orthogonal translation and protein engineering in semisynthetic eukaryotic cells.

PMID:
30923194
DOI:
10.1126/science.aaw2644

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