Ribosomal frameshifting at normal codon repeats recodes functional chimeric proteins in human

Abstract

Ribosomal frameshifting refers to the process that ribosomes slip into +1 or -1 reading frame, thus produce chimeric trans -frame proteins. In viruses and bacteria, programmed ribosomal frameshifting can produce essential trans -frame proteins for viral replication or regulation of other biological processes. In humans, ho w e v er, functional trans -frame protein derived from ribosomal frameshifting is scarcely documented. Combining multiple assa y s, w e sho w that short c odon r epeats could act as cis- acting elements that stimulate ribosomal f rames hifting in humans, abbreviated as CRFS hereafter. Using proteomic analyses, we identified many putative CRFS events from 32 normal human tissues supported by trans -frame peptides positioned at codon repeats. Finally, we show a CRFS-derived trans -frame protein (HD A C1-FS) functions by antagonizing the activities of HD A C1, thus affecting cell migration and apoptosis. These data suggest a no v el type of translational recoding associated with codon repeats, which may expand the coding capacity of mRNA and diversify the regulation in human.