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Type: Journal article
Title: Extensive transcriptional responses are co-ordinated by microRNAs as revealed by Exon-Intron Split Analysis (EISA)
Author: Pillman, K.A.
Scheer, K.G.
Hackett-Jones, E.
Saunders, K.
Bert, A.G.
Toubia, J.
Whitfield, H.J.
Sapkota, S.
Sourdin, L.
Pham, H.
Le, T.D.
Cursons, J.
Davis, M.J.
Gregory, P.A.
Goodall, G.J.
Bracken, C.P.
Citation: Nucleic Acids Research, 2019; 47(16)
Publisher: Oxford University Press
Issue Date: 2019
ISSN: 0305-1048
Statement of
Katherine A. Pillman, Kaitlin G. Scheer, Emily Hackett-Jones, Klay Saunders, Andrew G Bert, John Toubia, Holly J Whitfield, Sunil Sapkota, Laura Sourdin, Hoang Pham, Thuc D. Le, Joseph Cursons, Melissa J. Davis, Philip A. Gregory, Gregory J. Goodall and Cameron P. Bracken
Abstract: Epithelial-mesenchymal transition (EMT) has been a subject of intense scrutiny as it facilitates metastasis and alters drug sensitivity. Although EMT-regulatory roles for numerous miRNAs and transcription factors are known, their functions can be difficult to disentangle, in part due to the difficulty in identifying direct miRNA targets from complex datasets and in deciding how to incorporate 'indirect' miRNA effects that may, or may not, represent biologically relevant information. To better understand how miRNAs exert effects throughout the transcriptome during EMT, we employed Exon-Intron Split Analysis (EISA), a bioinformatic technique that separates transcriptional and post-transcriptional effects through the separate analysis of RNA-Seq reads mapping to exons and introns. We find that in response to the manipulation of miRNAs, a major effect on gene expression is transcriptional. We also find extensive co-ordination of transcriptional and post-transcriptional regulatory mechanisms during both EMT and mesenchymal to epithelial transition (MET) in response to TGF-β or miR-200c respectively. The prominent transcriptional influence of miRNAs was also observed in other datasets where miRNA levels were perturbed. This work cautions against a narrow approach that is limited to the analysis of direct targets, and demonstrates the utility of EISA to examine complex regulatory networks involving both transcriptional and post-transcriptional mechanisms.
Keywords: Cell Line
Epithelial Cells
Epidermal Growth Factor
Extracellular Signal-Regulated MAP Kinases
Transforming Growth Factor beta
RNA, Messenger
Computational Biology
Signal Transduction
Transcription, Genetic
RNA Processing, Post-Transcriptional
Proto-Oncogene Proteins c-akt
Gene Regulatory Networks
Epithelial-Mesenchymal Transition
Datasets as Topic
ErbB Receptors
Rights: © The Author(s) 2019. 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 License (, which permits unrestricted reuse, distribution, and reproduction in any medium, provided the original work is properly cited.
DOI: 10.1093/nar/gkz664
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