| RRC ID |
74900
|
| Author |
Kawasaki S, Ono H, Hirosawa M, Kuwabara T, Sumi S, Lee S, Woltjen K, Saito H.
|
| Title |
Programmable mammalian translational modulators by CRISPR-associated proteins.
|
| Journal |
Nat Commun
|
| Abstract |
Translational modulation based on RNA-binding proteins can be used to construct artificial gene circuits, but RNA-binding proteins capable of regulating translation efficiently and orthogonally remain scarce. Here we report CARTRIDGE (Cas-Responsive Translational Regulation Integratable into Diverse Gene control) to repurpose Cas proteins as translational modulators in mammalian cells. We demonstrate that a set of Cas proteins efficiently and orthogonally repress or activate the translation of designed mRNAs that contain a Cas-binding RNA motif in the 5'-UTR. By linking multiple Cas-mediated translational modulators, we designed and built artificial circuits like logic gates, cascades, and half-subtractor circuits. Moreover, we show that various CRISPR-related technologies like anti-CRISPR and split-Cas9 platforms could be similarly repurposed to control translation. Coupling Cas-mediated translational and transcriptional regulation enhanced the complexity of synthetic circuits built by only introducing a few additional elements. Collectively, CARTRIDGE has enormous potential as a versatile molecular toolkit for mammalian synthetic biology.
|
| Volume |
14(1)
|
| Pages |
2243
|
| Published |
2023-4-19
|
| DOI |
10.1038/s41467-023-37540-7
|
| PII |
10.1038/s41467-023-37540-7
|
| PMID |
37076490
|
| PMC |
PMC10115826
|
| MeSH |
Animals
CRISPR-Associated Proteins* / genetics
CRISPR-Cas Systems* / genetics
Gene Expression Regulation
Gene Regulatory Networks
Mammals / genetics
RNA, Messenger
|
| IF |
12.121
|
| Resource |
| Human and Animal Cells |
A549(RCB3677)
1383D6(HPS1006) |
