Annotation and functional clustering of circRNA expression in rhesus macaque brain during aging

Kaiyu Xu,Dong Chen,Jian Ma,Yi Zhang,Longbao Lv,Yongtang Zheng,Nanhui Chen,Jiali Li,Zhengbo Wang,Jian Zhou,Xintian Hu

doi:10.1038/s41421-018-0050-1

Kaiyu Xu, Dong Chen + Show 9 more

Open Access

https://doi.org/10.1038/s41421-018-0050-1

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Abstract

The abundance and function of circular RNAs (circRNAs) in mammalian brain have been reported, but their alterations in the biology of brain aging remain elusive. Here, using deep RNA profiling with linear RNA digestion by RNase R we explored a comprehensive map of changes in circRNA expression in rhesus macaque (macaca mulatta) brain in two age groups from adult (10 y) to aged (20 y) periods. Total 17,050 well expressed, stable circRNAs were identified. Cluster analysis reveals that dynamic changes in circRNA expression show the spatial-, sex- and age-biased specificities. On the basis of separate profiling of the RNAs, age-related circRNAs show differential correlation to host mRNA expression. Furthermore, two voltage-dependent L- and R-type calcium channel gene-derived circCACNA2D1 and circCACNA1E negatively regulate their host mRNA expression. Our results demonstrate the power of changes in circRNA expression to reveal insights into a potentially circRNA-mediated regulatory mechanism underlying the biology of brain aging.

Highlights

Aging leads to changes in brain function as well as many other physiological activities[1]
Our findings reveal that Circular RNA (circRNA) are highly abundant in rhesus macaque brain, and changes in circRNA expression show spatiotemporal- and sex-biased specificities during aging, and age-related circRNA correlate with their host mRNA expression
To systematically determine the pattern of circRNA expression in the rhesus macaque brain during aging, we deep-sequenced RNA samples with linear RNAs depleted from eight anatomical brain compartments including prefrontal cortex (PFC), posterior cingulate cortex (PCC), temporal cortex (TC), parietal cortex (PC) and occipital cortex (OC), hippocampus (CA1), and dentate gyrus (DG), and cerebellar cortex (CB) of rhesus macaque across the two ages (10 y and 20 y) (Supplementary Table S1)

Summary

Introduction

Aging leads to changes in brain function as well as many other physiological activities[1]. Brain aging is characterized by changes in the neuronal physiology, from molecular, to cell and functional levels[2]. Circular RNA (circRNA) is formed by head-to-tail splicing with the covalent joining the 5′ end of one exon with the 3′ end of another[10,11,12,13,14,15,16].

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