Research Article: CircRNAs in the tree shrew (Tupaia belangeri) brain during postnatal development and aging

Date Published: April 30, 2018

Publisher: Impact Journals

Author(s): CaiXia Lu, XiaoMei Sun, Na Li, WenGuang Wang, DeXuan Kuang, PinFen Tong, YuanYuan Han, JieJie Dai.


Circular RNAs (circRNAs) are a novel type of non-coding RNA expressed across different species and tissues. At present, little is known about the expression and function of circRNAs in the tree shrew brain. In this study, we used RNA-seq to identify 35,007 circRNAs in hippocampus and cerebellum samples from infant (aged 47–52 days), young (aged 15–18 months), and old (aged 78–86 months) tree shrews. We observed no significant changes in the total circRNA expression profiles in different brain regions over time. However, circRNA tended to be downregulated in the cerebellum over time. Real-time RT-PCR analysis verified the presence of circRNAs. KEGG analysis indicated the occurrence of ubiquitin-mediated proteolysis, the MAPK signaling pathway, phosphatidylinositol signaling system, long-term depression, the rap1 signaling pathway, and long-term potentiation in both brain regions. We also observed that 29,087 (83.1%) tree shrew circRNAs shared homology with human circRNAs. The competing endogenous RNA networks suggested novel_circRNA_007362 potential functions as a 24-miRNAs sponge to regulate UBE4B expression. Thus, we obtained comprehensive circRNA expression profiles in the tree shrew brain during postnatal development and aging, which might help to elucidate the functions of circRNAs during brain aging and in age-related diseases.

Partial Text

Circular RNAs (circRNAs) are a novel type of non-coding RNA with a covalently closed-loop structure generated by back splicing. CircRNAs were first identified approximately 37 years ago [1], but they have only recently attracted the attention of researchers. CircRNAs are considerably more stable and more resistant to RNase R than linear RNAs [2]. However, the functions of most circRNAs remain unclear. Previous studies have shown circRNAs can act as “sponges” for microRNAs via the competing endogenous RNA (ceRNA) network in order to regulate target gene expression [3,4]. CircRNAs may also serve as sponges for RNA-binding proteins to post-transcriptionally modulate mRNA expression [4].

In the present study, we identified 35,007 circRNAs in the tree shrew brain using high-throughput sequencing. We found that most of the circRNAs measured approximately 400 nt in length, as also reported in previous studies [29]. In the tree shrew, the major circRNAs were annot_exon, whereas in the sheep pituitary, the major circRNAs were intergenic [13]. This finding may suggest that the distribution of circRNAs can exhibit species and tissue specificity.




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