RT Journal Article SR Electronic T1 Tunable protein synthesis by transcript isoforms in human cells JF bioRxiv FD Cold Spring Harbor Laboratory SP 035188 DO 10.1101/035188 A1 Stephen N. Floor A1 Jennifer A. Doudna YR 2015 UL http://biorxiv.org/content/early/2015/12/23/035188.abstract AB Eukaryotic genes generate multiple mRNA transcript isoforms though alternative transcription, splicing, and polyadenylation. However, the relationship between human transcript diversity and protein production is complex and not well understood at a global level. We fractionated a polysome profile and reconstructed transcript isoforms from each fraction, which we term Transcript Isoforms in Polysomes sequencing (TrIP-seq). Analysis of these data revealed regulatory features that control ribosome occupancy and the resulting translational output of each transcript isoform. We extracted a panel of 5′ and 3′ untranslated regions that control protein production from an unrelated gene in cells over a 100-fold range. Select 5′ untranslated regions exert robust translational control between cell lines, while 3′ untranslated regions can confer cell-type-specific expression. These results expose the large dynamic range of transcript-isoform-specific translational control, identify isoform-specific sequences that control protein output in human cells, and demonstrate that transcript isoform diversity must be considered when relating RNA and protein levels.