PT  - JOURNAL ARTICLE
AU  - Stephen N. Floor
AU  - Jennifer A. Doudna
TI  - Tunable protein synthesis by transcript isoforms in human cells
AID  - 10.1101/035188
DP  - 2015 Jan 01
TA  - bioRxiv
PG  - 035188
4099  - http://biorxiv.org/content/early/2015/12/23/035188.short
4100  - http://biorxiv.org/content/early/2015/12/23/035188.full
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.