Rat BodyMap transcriptomes reveal unique circular RNA features across tissue types and developmental stages

Abstract

24Circular RNAs (circRNAs) are a novel class of regulatory RNAs. Here, we present a 25 comprehensive investigation of circRNA expression profiles across 11 tissues and 4 26 developmental stages in rats, along with cross-species analyses in humans and mice. Although 27 the expression of circRNAs is positively correlated with that of cognate mRNAs, highly 28 expressed genes tend to splice a larger fraction of circular transcripts. Moreover, circRNAs 29 exhibit higher tissue specificity than cognate mRNAs. Intriguingly, while we observed a 30 monotonic increase of circRNA abundance with age in the rat brain, we further discovered a 31 dynamic, age-dependent pattern of circRNA expression in the testes that is characterized by a 32 dramatic increase with advancing stages of sexual maturity and a decrease with aging. The age-33 sensitive testicular circRNAs are highly associated with spermatogenesis, independent of cognate 34 mRNA expression.

Histone Post-Translational Modifications and CircRNAs in Mouse and Human Spermatozoa: Potential Epigenetic Marks to Assess Human Sperm Quality

“…The large number, especially in round SPT, allows to hypothesize an important control of circRNAs in SPT maturation [258]. Such an evidence has been strongly supported by the analysis of Rat Body Map transcriptome [259]. CircRNA repertoire has been scanned in 11 rat tissues and 4 developmental stages demonstrating that (i) circRNAs are evolutionary more conserved than linear mRNAs; (ii) circRNAs have higher tissue-specificity than mRNAs; (iii) in testis, circRNA expression dynamically changes depending on the age: it increases with sexual maturity and decreases with ageing.…”

“…However, circRNA biogenesis in tissues has been suggested as essential for that tissue performance, thus brain-specific circRNAs have been associated to "chemical synaptic transmission" as well as in testis they have been associated to "sperm motility acquisition" and "spermatid development". Additionally, as brain, testis seems to be a very sensitive organ with age-dependent changes in circRNA levels, thus to suggest that these molecules may be harnessed as biomarkers for reproductive ageing [259]. Together with intratesticular production of circRNAs, testis-derived circRNAs stably exist in seminal plasma, probably in the form of protein-complexes, thus to strongly suggest their application as novel non-invasive biomarkers for male fertility [253].…”

“…Despite that circRNAs have been identified in both mammalian testis and seminal plasma [253,258,259] and several lines of evidence have pointed to establish a potential role for these molecules in mammalian embryo development, a missing puzzle piece concerns a possible circRNA landscape in mature SPZ. Very recently, our group-for the first time-has drawn a complete payload of circRNAs in human SPZ, analyzing all the characteristics concerning these molecules by using bioinformatic approaches [265].…”

The Function of Pre-mRNA Alternative Splicing in Mammal Spermatogenesis

“…Circular RNAs (circRNAs), unlike miRNAs and long non-coding RNAs (lncRNAs), are a novel type of non-coding RNAs originated from introns, intergenic regions, untranslated regions and exhibit distinct patterns of alternative back-splicing and alternative splicing [107,108]. The roles of circRNAs in self-renewal and differentiation of spermatogonial stem cells and sperm motility are gradually being studied [109][110][111][112]. However, the relationships between alternative splicing that involved by circRNAs and spermatogenesis was seldom reported and needed further study.…”

Current status and potential role of circular RNAs in neurological disorders

“…CircRNAs are widely distributed in various organ systems such as the heart, brain, liver, lung, kidney, skin, and blood, and their expression is typically tissue‐ and development‐specific (Memczak et al ; Szabo et al ; Xia et al ; Maass et al ; Zhou et al ; Zaghlool et al ). In particular, circRNAs are highly enriched in neuronal tissues (Westholm et al ; Rybak‐Wolf et al ; You et al ).…”