Expression of a Human CDNA in Moss Results in Spliced MRNAs and Fragmentary Protein Isoforms

Overview

Journal Commun Biol

Specialty Biology

Date 2021 Aug 13

PMID 34385580

Citations 8

Authors

Oguz Top

Stella W L Milferstaedt

Nico van Gessel

Sebastian N W Hoernstein

Bugra Ozdemir

Eva L Decker

Ralf Reski

Affiliations

Soon will be listed here.

Abstract

Production of biopharmaceuticals relies on the expression of mammalian cDNAs in host organisms. Here we show that the expression of a human cDNA in the moss Physcomitrium patens generates the expected full-length and four additional transcripts due to unexpected splicing. This mRNA splicing results in non-functional protein isoforms, cellular misallocation of the proteins and low product yields. We integrated these results together with the results of our analysis of all 32,926 protein-encoding Physcomitrella genes and their 87,533 annotated transcripts in a web application, physCO, for automatized optimization. A thus optimized cDNA results in about twelve times more protein, which correctly localizes to the ER. An analysis of codon preferences of different production hosts suggests that similar effects occur also in non-plant hosts. We anticipate that the use of our methodology will prevent so far undetected mRNA heterosplicing resulting in maximized functional protein amounts for basic biology and biotechnology.

Citing Articles

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