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Comprehensive survey of human brain microRNA by deep sequencing

Shao, Ning-Yi, Hu, Hai Yang, Yan, Zheng, Xu, Ying, Hu, Hao, Menzel, Corinna, Li, Na, Chen, Wei, Khaitovich, Philipp·2010·BMC Genomics
DOI 10.1186/1471-2164-11-409PMC PMC2996937
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Abstract

Background: MicroRNA (miRNA) play an important role in gene expression regulation. At present, the number of annotated miRNA continues to grow rapidly, in part due to advances of high-throughput sequencing techniques. Here, we use deep sequencing to characterize a population of small RNA expressed in human and rhesus macaques brain cortex. Results: Based on a total of more than 150 million sequence reads we identify 197 putative novel miRNA, in humans and rhesus macaques, that are highly conserved among mammals. These putative miRNA have significant excess of conserved target sites in genes' 3'UTRs, supporting their functional role in gene regulation. Additionally, in humans and rhesus macaques respectively, we identify 41 and 22 conserved putative miRNA originating from non-coding RNA (ncRNA) transcripts. While some of these molecules might function as conventional miRNA, others might be harmful and result in target avoidance. Conclusions: Here, we further extend the repertoire of conserved human and rhesus macaque miRNA. Even though our study is based on a single tissue, the coverage depth of our study allows identification of functional miRNA present in brain tissue at background expression levels. Therefore, our study might cover large proportion of the yet unannotated conserved miRNA present in the human genome.

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Figure 1 Expression levels of conserved annotated and putative miRNA. Distribution of expression levels (base-10 logarithm transformed) of conserved annotated miRNA (Am/green), conserved putative miRNA, excluding the ones originating from ncRNA (Pm/red), and conserved putative miRNA originating from ncRNA (Pn/blue) in humans (A) and rhesus macaques (B).
Figure 1 Expression levels of conserved annotated and putative miRNA. Distribution of expression levels (base-10 logarithm transformed) of conserved annotated miRNA (Am/green), conserved putative miRNA, excluding the ones originating from ncRNA (Pm/red), and conserved putative miRNA originating from ncRNA (Pn/blue) in humans (A) and rhesus macaques (B).CC BY · PubMed Central
Figure 2 Conservation of human annotated and putative miRNA. The distribution of average sequence conservation scores (phastCon scores) based on alignment of 18 placental mammalian genomes within annotated human miRNA (Am/green), novel putative miRNA that passed our pipeline, excluding the ncRNA-derived miRNA (Pm/red), and the background phastCon scores distribution (Bg/grey) based on 1,000 simulations (see Methods for details). The error bars show 95% confidence interval of the background phastCon scores distribution. Shown are the proportions (A) and the numbers (B) of miRNA in each of the 10 phastCon score bins (between 0 and 1, from the least conserved to the most conserved, divided into equal intervals).
Figure 2 Conservation of human annotated and putative miRNA. The distribution of average sequence conservation scores (phastCon scores) based on alignment of 18 placental mammalian genomes within annotated human miRNA (Am/green), novel putative miRNA that passed our pipeline, excluding the ncRNA-derived miRNA (Pm/red), and the background phastCon scores distribution (Bg/grey) based on 1,000 simulations (see Methods for details). The error bars show 95% confidence interval of the background phastCon scores distribution. Shown are the proportions (A) and the numbers (B) of miRNA in each of the 10 phastCon score bins (between 0 and 1, from the least conserved to the most conserved, divided into equal intervals).CC BY · PubMed Central
Figure 3 Target site conservation excess of annotated and putative miRNA. The proportion of seed families with target site conservation excess (p < 0.05) among annotated conserved miRNA (Am/green), putative conserved miRNA excluding ncRNA-derived miRNA (Pm/red), and ncRNA-derived putative conserved miRNA identified in human dataset (A) and overlapping between human and rhesus datasets (B). The background proportion (Bg/grey) was calculated by 1,000 random simulations of seed region sequences (see Methods for details). The error bars show 95% confidence interval of the simulations. The stars above the bars (**) indicate significance level based on the simulation results.
Figure 3 Target site conservation excess of annotated and putative miRNA. The proportion of seed families with target site conservation excess (p < 0.05) among annotated conserved miRNA (Am/green), putative conserved miRNA excluding ncRNA-derived miRNA (Pm/red), and ncRNA-derived putative conserved miRNA identified in human dataset (A) and overlapping between human and rhesus datasets (B). The background proportion (Bg/grey) was calculated by 1,000 random simulations of seed region sequences (see Methods for details). The error bars show 95% confidence interval of the simulations. The stars above the bars (**) indicate significance level based on the simulation results.CC BY · PubMed Central

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Cites

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Metadata

Authors
Shao, N.-Y., Hu, H. Y., Yan, Z., Xu, Y., Hu, H., Menzel, C., Li, N., Chen, W., & Khaitovich, P.
Venue
BMC Genomics
Publisher
Springer Science and Business Media LLC
Published
2010-06-30
Volume
11
Issue
1
ISSN
1471-2164
DOI
10.1186/1471-2164-11-409
PMC
PMC2996937
Cited by
131
References
3
Language
en

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