@article {Floor035188, author = {Stephen N. Floor and Jennifer A. Doudna}, title = {Tunable protein synthesis by transcript isoforms in human cells}, elocation-id = {035188}, year = {2015}, doi = {10.1101/035188}, publisher = {Cold Spring Harbor Laboratory}, abstract = {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.}, URL = {https://www.biorxiv.org/content/early/2015/12/23/035188}, eprint = {https://www.biorxiv.org/content/early/2015/12/23/035188.full.pdf}, journal = {bioRxiv} }