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

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.

SUBMITTER: Reinkemeier CD

PROVIDER: S-EPMC7611745 | biostudies-literature | 2019 Mar

REPOSITORIES: biostudies-literature

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

Reinkemeier Christopher D CD Girona Gemma Estrada GE Lemke Edward A EA

Science (New York, N.Y.) 20190301 6434

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 ...[more]

PMID: 30923194

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