The Establishment of Artificial RNA Cascade Circuits for Gene Regulation Based on Doxycycline-Induced Pre-mRNA Alternative Splicing.

ABSTRACT: This study developed an artificial chimeric intron module with an RNA riboswitch and TetR aptamer that were integrated into essential gene exons. Doxycycline can modulate Pre-mRNA alternative splicing, modify the exon reading frame, and dynamically regulate gene expression. By shifting the aptamer 2 base pair within the switch, we unexpectedly obtained the "on-switch" CTM and "off-switch" C2ITetR>4A, which possess thoroughly contrasting regulatory functions. The CTM module can conditionally induce tumor cell apoptosis and regulate genes reversibly and sustainably following doxycycline induction. We integrated the C2ITetR>4A/CTM switches with the L7Ae/k-turn module to create an intron-spliced double-switched RNA cascade system. The system can both activate and inhibit the splicing mechanism

SUBMITTER: Dai G 

PROVIDER: S-EPMC11817826 | biostudies-literature | 2025 Jan

REPOSITORIES: biostudies-literature