Eberly College of Arts and Sciences
Alternative first exons diversify the transcriptomes of eukaryotes by producing variants of the 5′ Untrans- lated Regions (5′UTRs) and N-terminal coding se- quences. Accurate transcriptome-wide detection of alternative first exons typically requires specialized experimental approaches that are designed to iden- tify the 5′ ends of transcripts. We developed a compu- tational pipeline SEASTAR that identifies first exons from RNA-seq data alone then quantifies and com- pares alternative first exon usage across multiple bi- ological conditions. The exons inferred by SEASTAR coincide with transcription start sites identified di- rectly by CAGE experiments and bear epigenetic hall- marks of active promoters. To determine if differen- tial usage of alternative first exons can yield insights into the mechanism controlling gene expression, we applied SEASTAR to an RNA-seq dataset that tracked the reprogramming of mouse fibroblasts into in- duced pluripotent stem cells. We observed dynamic temporal changes in the usage of alternative first ex- ons, along with correlated changes in transcription factor expression. Using a combined sequence mo- tif and gene set enrichment analysis we identified N-Myc as a regulator of alternative first exon usage in the pluripotent state. Our results demonstrate that SEASTAR can leverage the available RNA-seq data to gain insights into the control of gene expression and alternative transcript variation in eukaryotic tran- scriptomes.
Digital Commons Citation
Qin, Zhiyi; Stoilov, Peter; Zhang, Xuegong; and Xing, Yi, "SEASTAR: systematic evaluation of alternative transcription start sites in RNA" (2018). Faculty & Staff Scholarship. 1619.
Qin, Z., Stoilov, P., Zhang, X., & Xing, Y. (2018). SEASTAR: systematic evaluation of alternative transcription start sites in RNA. Nucleic Acids Research, 46(8), e45–e45. https://doi.org/10.1093/nar/gky053