Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
. 2019 Feb 22;9(1):2564.
doi: 10.1038/s41598-019-38860-9.

Circular RNAs are temporospatially regulated throughout development and ageing in the rat

E Mahmoudi  1   2   3 , M J Cairns  4   5   6
Affiliations

Circular RNAs are temporospatially regulated throughout development and ageing in the rat

E Mahmoudi et al. Sci Rep. .

Abstract

Circular RNAs (circRNAs) are covalently closed structural isoforms of linear mRNA which have been observed across a broad range of species and tissues. Here, we provide a comprehensive circRNAs expression catalogue for the rat including 8 organs of both sexes during 4 developmental stages using a public RNAseq dataset. These analyses revealed thousands of circular RNA species, many expressed in an organ-specific manner along with their host genes which were enriched with tissue-specific biological functions. A large number of circRNAs also displayed a developmental-dependent expression pattern and are accumulated during ageing. CircRNAs also displayed some sexually dimorphic expression, with gender associated differences observed in various tissues and developmental stages. These observations suggest that circRNAs are dynamically expressed in a spatial-, temporal- and gender-specific manner in mammals, and may have important biological function in differentiation, development and aging.

PubMed Disclaimer

Conflict of interest statement

The authors declare no competing interests.

Figures

Figure 1
Figure 1
Comprehensive landscape of circRNAs in rat. (A) Schematic illustration of the computational pipeline used to identify circRNAs. (B) Number of circRNAs detected in rat categorized by organ. (C) classification of the discovered circRNAs by genomic features. (D) Distributions of gene numbers for circRNAs in each organ. (E) Distributions of exon numbers for circRNAs in each organ. (F) Top 4 chromosomes with the largest number of circRNAs in each organ.
Figure 2
Figure 2
Analysis of circRNAs expression across development. (A) Scatter plot of circRNAs fold changes between 2- week old and 104-week old rats. (B) Heatmap comparison of circRNAs expression across 4 developmental time points. The abundance is depicted on a scale from red (low expression) to yellow (high expression). (C) Average expression of circRNA at 4 developmental stages calculated in RPM values (reads per million mapped reads) and ANOVA test for all the stages.
Figure 3
Figure 3
Development-dependent expression of circRNAs in rat organs. (A) Differential Expression analysis of circRNA between 4 developmental time points from 2-week old to 104-week old for 8 organs based (Wilcoxon test, P-value < 0.05 and FC >2).
Figure 4
Figure 4
Pairwise comparison of circRNAs between different organs. (A) Number of circRNAs overlapped between any two rat organs. (B) Euclidean distance for circRNAs based on number of shared circRNAs between different organs.
Figure 5
Figure 5
Gene Ontology enrichment analysis of circRNAs host genes. (A) The scatter plot of GO clusters significantly enriched in brain. (B) The scatter plot of GO clusters significantly enriched in heart. The scatter plot indicates the clusters (after redundancy filtration) in a two-dimensional space by applying multi-dimensional scaling to a matrix of GO terms semantic similarities. The color of bubble shows corrected P-value and the size of circle represents the frequency of the GO term in the GOA database.
Figure 6
Figure 6
CircRNA and mRNA expression changes. (A) Comparisons of circRNAs expression change between initial and final developmental stages to the mRNA counterparts at the same developmental stages. (B) Barplots comparing the percentage of circRNAs differentially expressed (FC >2) between 2-week and 104-week old rats to the mRNA counterparts in each organ. Green bars represent upregulation and red indicated downregulation.
Figure 7
Figure 7
Sex differences of circRNA pattern in rat. CircRNAs expression (log2 RPM values) for both genders are plotted using pooled data of seven organs in each developmental stage. The red points with circRAN names are significantly expressed circRNAs between male and female.
Figure 8
Figure 8
Prediction of interaction network of circRNA-miRNA-mRNA. (A) Interaction network of age-accumulated circRNAs with developmentally increased mRNAs via targeting miRNAs. Purple Circles represent circRNA, pink triangles miRNA and green rectangles mRNA. (B) Correlation between the expression levels of circRNA and mRNA targets at 4 different developmental stages.
See this image and copyright information in PMC

References

    1. Ebbesen KK, Kjems J, Hansen TB. Circular RNAs: Identification, biogenesis and function. Biochim Biophys Acta. 2016;1859:163–168. doi: 10.1016/j.bbagrm.2015.07.007. - DOI - PubMed
    1. Chen LL. The biogenesis and emerging roles of circular RNAs. Nat Rev Mol Cell Biol. 2016;17:205–211. doi: 10.1038/nrm.2015.32. - DOI - PubMed
    1. Jeck WR, Sharpless NE. Detecting and characterizing circular RNAs. Nat Biotechnol. 2014;32:453–461. doi: 10.1038/nbt.2890. - DOI - PMC - PubMed
    1. Ivanov A, et al. Analysis of intron sequences reveals hallmarks of circular RNA biogenesis in animals. Cell Rep. 2015;10:170–177. doi: 10.1016/j.celrep.2014.12.019. - DOI - PubMed
    1. Conn SJ, et al. The RNA binding protein quaking regulates formation of circRNAs. Cell. 2015;160:1125–1134. doi: 10.1016/j.cell.2015.02.014. - DOI - PubMed

Publication types