Document Type

Article

Publication Date

2018

College/Unit

Eberly College of Arts and Sciences

Department/Program/Center

Biochemistry

Abstract

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.

Source Citation

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

Comments

⃝C The Author(s) 2018. Published by Oxford University Press on behalf of Nucleic Acids Research. This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/4.0/), which permits non-commercial re-use, distribution, and reproduction in any medium, provided the original work is properly cited. For commercial re-use, please contact journals.permissions@oup.com

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