Terminal exon characterization with TECtool reveals an abundance of cell-specific isoforms

Sequencing of RNA 3’ ends uncovered numerous sites that do not correspond to termination sites of known transcripts. Through their 3’ untranslated regions, protein-coding RNAs interact with RNA-binding proteins and microRNAs, which regulate many properties, including RNA stability and subcellular localization. Here we present the ‘terminal exon characterization’ (TEC) tool (http://tectool.unibas.ch), applicable to RNA sequencing data from any species for which a genome annotation that includes sites of RNA cleavage and polyadenylation is available. We describe hundreds of novel isoforms and cell type-specific terminal exons in human cells. Ribosome profiling data indicate that many of these isoforms are translated. Applying TECtool to single cell sequencing data we find that the newly identified isoforms have typical per-cell abundance, but are expressed in subpopulations of cells. Thus, TECtool enables identification of novel isoforms in well studied cell systems and in rare cell types.