Alicia A Bicknell, David W Reid, Marissa C Licata, Adriana K Jones, Yi Min Cheng, Mengying Li, Chiaowen Joyce Hsiao, Christopher S Pepin, Mihir Metkar, Yevgen Levdansky, Brian R Fritz, Elizaveta A Andrianova, Ruchi Jain, Eugene Valkov, Caroline Köhrer, Melissa J Moore
Developing an effective mRNA therapeutic often requires maximizing protein output per delivered mRNA molecule. We previously found that coding sequence (CDS) design can substantially affect protein output, with mRNA variants containing more optimal codons and higher secondary structure yielding the highest protein outputs due to their slow rates of mRNA decay. Here, we demonstrate that CDS-dependent differences in translation initiation and elongation rates lead to differences in translation- and deadenylation-dependent mRNA decay rates, thus explaining the effect of CDS on mRNA half-life...
April 15, 2024: Cell Reports