Toward the human cellular microRNAome
- Matthew N. McCall1,
- Min-Sik Kim2,3,
- Mohammed Adil4,
- Arun H. Patil3,5,6,7,
- Yin Lu8,
- Christopher J. Mitchell9,
- Pamela Leal-Rojas10,
- Jinchong Xu11,12,
- Manoj Kumar11,12,
- Valina L. Dawson11,12,13,14,
- Ted M. Dawson11,12,13,15,
- Alexander S. Baras8,
- Avi Z. Rosenberg8,
- Dan E. Arking3,
- Kathleen H. Burns3,8,
- Akhilesh Pandey3 and
- Marc K. Halushka8
- 1Department of Biostatistics and Computational Biology, University of Rochester Medical Center, Rochester, New York 14642, USA;
- 2Department of Applied Chemistry, Kyung Hee University, Yongin, Gyeonggi 17104, South Korea 3;
- 3McKusick-Nathans Institute of Genetic Medicine, Johns Hopkins University School of Medicine, Baltimore, Maryland 21205, USA;
- 4Department School of Life Sciences, B.S. Abdur Rahman University, Chennai, 600048, India;
- 5School of Biotechnology, KIIT University, Bhubaneswar, Odisha, 751024, India;
- 6Institute of Bioinformatics, International Technology Park, Bangalore, 560066, India;
- 7YU-IOB Center for Systems Biology and Molecular Medicine, Yenepoya University, Mangalore, 575018, India;
- 8Department of Pathology, Johns Hopkins University School of Medicine, Baltimore, Maryland 21205, USA;
- 9Ginkgo Bioworks, Boston, Massachusetts 02210, USA;
- 10Center of Excellence in Translational Medicine (CEMT) & Scientific and Technological Bioresource Nucleus (BIOREN), Universidad de La Frontera, 4810296 Temuco, Chile;
- 11Neuroregeneration and Stem Cell Programs, Institute for Cell Engineering, Johns Hopkins University School of Medicine, Baltimore, Maryland 21205, USA;
- 12Department of Neurology, Johns Hopkins University School of Medicine, Baltimore, Maryland 21205, USA;
- 13Solomon H. Snyder Department of Neuroscience, Johns Hopkins University School of Medicine, Baltimore, Maryland 21205, USA;
- 14Department of Physiology, Johns Hopkins University School of Medicine, Baltimore, Maryland 21205, USA;
- 15Department of Pharmacology and Molecular Sciences, Johns Hopkins University School of Medicine, Baltimore, Maryland 21205, USA
Abstract
MicroRNAs are short RNAs that serve as regulators of gene expression and are essential components of normal development as well as modulators of disease. MicroRNAs generally act cell-autonomously, and thus their localization to specific cell types is needed to guide our understanding of microRNA activity. Current tissue-level data have caused considerable confusion, and comprehensive cell-level data do not yet exist. Here, we establish the landscape of human cell-specific microRNA expression. This project evaluated 8 billion small RNA-seq reads from 46 primary cell types, 42 cancer or immortalized cell lines, and 26 tissues. It identified both specific and ubiquitous patterns of expression that strongly correlate with adjacent superenhancer activity. Analysis of unaligned RNA reads uncovered 207 unknown minor strand (passenger) microRNAs of known microRNA loci and 495 novel putative microRNA loci. Although cancer cell lines generally recapitulated the expression patterns of matched primary cells, their isomiR sequence families exhibited increased disorder, suggesting DROSHA- and DICER1-dependent microRNA processing variability. Cell-specific patterns of microRNA expression were used to de-convolute variable cellular composition of colon and adipose tissue samples, highlighting one use of these cell-specific microRNA expression data. Characterization of cellular microRNA expression across a wide variety of cell types provides a new understanding of this critical regulatory RNA species.
Footnotes
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[Supplemental material is available for this article.]
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Article published online before print. Article, supplemental material, and publication date are at http://www.genome.org/cgi/doi/10.1101/gr.222067.117.
- Received February 28, 2017.
- Accepted August 7, 2017.
This article is distributed exclusively by Cold Spring Harbor Laboratory Press for the first six months after the full-issue publication date (see http://genome.cshlp.org/site/misc/terms.xhtml). After six months, it is available under a Creative Commons License (Attribution-NonCommercial 4.0 International), as described at http://creativecommons.org/licenses/by-nc/4.0/.
