Synonymous modification results in high-fidelity gene expression of repetitive protein and nucleotide sequences.

ABSTRACT: Repetitive nucleotide or amino acid sequences are often engineered into probes and biosensors to achieve functional readouts and robust signal amplification. However, these repeated sequences are notoriously prone to aberrant deletion and degradation, impacting the ability to correctly detect and interpret biological functions. Here, we introduce a facile and generalizable approach to solve this often unappreciated problem by modifying the nucleotide sequences of the target mRNA to make them nonrepetitive but still functional ("synonymous"). We first demonstrated the procedure by designing a cassette of synonymous MS2 RNA motifs and tandem coat proteins for RNA imaging and showed a dramatic improvement in signal and reproducibility in single-RNA detection in live cells. The same approach w

SUBMITTER: Wu B 

PROVIDER: S-EPMC4403262 | biostudies-literature | 2015 Apr

REPOSITORIES: biostudies-literature