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Genome Res. 2017 Oct;27(10):1769-1781. doi: 10.1101/gr.222067.117. Epub 2017 Sep 6.

Toward the human cellular microRNAome.

Author information

1
Department of Biostatistics and Computational Biology, University of Rochester Medical Center, Rochester, New York 14642, USA.
2
Department of Applied Chemistry, Kyung Hee University, Yongin, Gyeonggi 17104, South Korea 3.
3
McKusick-Nathans Institute of Genetic Medicine, Johns Hopkins University School of Medicine, Baltimore, Maryland 21205, USA.
4
Department School of Life Sciences, B.S. Abdur Rahman University, Chennai, 600048, India.
5
School of Biotechnology, KIIT University, Bhubaneswar, Odisha, 751024, India.
6
Institute of Bioinformatics, International Technology Park, Bangalore, 560066, India.
7
YU-IOB Center for Systems Biology and Molecular Medicine, Yenepoya University, Mangalore, 575018, India.
8
Department of Pathology, Johns Hopkins University School of Medicine, Baltimore, Maryland 21205, USA.
9
Ginkgo Bioworks, Boston, Massachusetts 02210, USA.
10
Center of Excellence in Translational Medicine (CEMT) & Scientific and Technological Bioresource Nucleus (BIOREN), Universidad de La Frontera, 4810296 Temuco, Chile.
11
Neuroregeneration and Stem Cell Programs, Institute for Cell Engineering, Johns Hopkins University School of Medicine, Baltimore, Maryland 21205, USA.
12
Department of Neurology, Johns Hopkins University School of Medicine, Baltimore, Maryland 21205, USA.
13
Solomon H. Snyder Department of Neuroscience, Johns Hopkins University School of Medicine, Baltimore, Maryland 21205, USA.
14
Department of Physiology, Johns Hopkins University School of Medicine, Baltimore, Maryland 21205, USA.
15
Department 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.

PMID:
28877962
PMCID:
PMC5630040
DOI:
10.1101/gr.222067.117
[Indexed for MEDLINE]
Free PMC Article

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