Repurposing The Dark Genome. III - Intronic Proteins

Abstract Based on the expression patterns, genomes are viewed as a collection of protein-coding, RNA-coding, and non-expressing DNA sequences. Unlike most prokaryotes, eukaryotic gene expression comes with an additional step called alternative splicing. During the maturation process, different combinations of exons are spliced out and joined together resulting in the formation of mRNA isoforms. After removal from pre-mRNA, introns may be degraded by cellular exonucleases or form long non-coding RNAs (lncRNAs), or temporarily retained in the nucleus for regulating gene expression. We asked: Do introns have an unutilized potential for encoding proteins? If introns had an opportunity of getting translated, what kind of peptides or proteins, would they make? This study is based on the hypothesis of making functional proteins from leftover introns and is an extension of the original work of making functional proteins from the E. coli intergenic sequences (Dhar et al., 2009). Here full-length introns were computationally translated into proteins to study their potential structural, physicochemical, functional, and cellular location properties. Experimental validation is underway for a detailed understanding of the biology of intronic proteins. A synthetic intronic protein repository would provide an opportunity to design first-in-the-class molecules toward functional endpoints.