Programmable mutually exclusive alternative splicing for generating RNA and protein diversity.

ABSTRACT: Alternative splicing performs a central role in expanding genomic coding capacity and proteomic diversity. However, programming of splicing patterns in engineered biological systems remains underused. Synthetic approaches thus far have predominantly focused on controlling expression of a single protein through alternative splicing. Here, we describe a modular and extensible platform for regulating four programmable exons that undergo a mutually exclusive alternative splicing event to generate multiple functionally-distinct proteins. We present an intron framework that enforces the mutual exclusivity of two internal exons and demonstrate a graded series of consensus sequence elements of varying strengths that set the ratio of two mutually exclusive isoforms. We apply this framework to progr

SUBMITTER: Mathur M 

PROVIDER: S-EPMC6572816 | biostudies-literature | 2019 Jun

REPOSITORIES: biostudies-literature