Orthogonal Protein-Responsive mRNA Switches for Mammalian Synthetic Biology

The lack of available genetic modules is a fundamental issue in mammalian synthetic biology. Especially, the variety of genetic parts for translational control are limited. Here we report a new set of synthetic mRNA-based translational switches by engineering RNA-binding proteins (RBPs) and RBP-binding RNA motifs (aptamers) that perform strong translational repression. We redesigned the RNA motifs with RNA scaffolds and improved the efficiency of the repression to target RBPs. Using new and previously reported mRNA switches, we demonstrated that the orthogonality of translational regulation was ensured among five different RBP-responsive switches. Moreover, the new switches functioned not only with plasmid introduction, but also with RNA-only delivery, which provides a transient and safer regulation of expression. The translational regulators using RNA-protein interactions provide an alternative strategy to construct complex genetic circuits for future cell engineering and therapeutics.

Medienart:

E-Artikel

Erscheinungsjahr:

2020

Erschienen:

2020

Enthalten in:

Zur Gesamtaufnahme - volume:9

Enthalten in:

ACS synthetic biology - 9(2020), 1 vom: 17. Jan., Seite 169-174

Sprache:

Englisch

Beteiligte Personen:

Ono, Hiroki [VerfasserIn]
Kawasaki, Shunsuke [VerfasserIn]
Saito, Hirohide [VerfasserIn]

Links:

Volltext

Themen:

Aptamer
Aptamers, Nucleotide
Gene switch
Journal Article
Mammalian synthetic biology
RNA, Messenger
RNA−protein interaction
RNA switch
RNA-Binding Proteins
Research Support, Non-U.S. Gov't
Translation

Anmerkungen:

Date Completed 25.01.2021

Date Revised 25.01.2021

published: Print-Electronic

Citation Status MEDLINE

doi:

10.1021/acssynbio.9b00343

funding:

Förderinstitution / Projekttitel:

PPN (Katalog-ID):

NLM30367962X