Pig transcriptome analysis suggests a global regulation mechanism enabling temporary bursts of circular RNAs
Résumé
Although the functions of most of circular RNAs (circRNAs) are not characterized, they likely impact many biological processes. Indeed, in addition to generating a linear transcript many protein-coding genes produce circRNAs that are tightly regulated.By analyzing Total-RNaseq from 7 pubertal testis samples we detected 126 introns in 114 genes able to produce intronic circRNAs and 5,236 exonic circRNAs produced by 2,516 genes. Comparison of Total-RNaseq data sets from porcine testis, embryonic cortex and postnatal muscle stages revealed a high abundance of intronic and exonic circRNAs for 2 samples from pubertal testis and embryonic cortex, respectively. In pubertal testis with circRNAs in abundance, 24% of protein-coding genes produced linear and circular transcripts. This abundance was due to higher production of circRNA by the same genes than in other testis samples rather than to the recruitment of new genes. No global relationship between exonic circRNA and mRNA productions was found in pubertal testis. We showed that exonic circRNAs are typically produced by large genes that are also able to produce mRNAs. We suggest ExoCirc-9244 (origin: SMARCA5) to be a marker of circRNA abundance in testis. Among 76 pubertal testes analyzed by RT-PCR, we identified 12 transcriptomes containing a large quantity of ExoCirc-9244 and which are therefore suspected to have an overall high circRNAs abundance. By qRT-PCR, we confirmed results concerning ExoCirc-9244 and showed that samples expressing ExoCirc-9244 had low steroid synthesis potential (confirmed by plasma estradiol level).Even though our data indicate that this massive production of circRNAs is much more related to the structure of genes generating circRNAs than to their function, we highlighted with ExoCirc-9244, a particular stage of pubertal testis development characterized by a low steroid production and an abundance of circRNA. We suggest that bursts of circRNAs might be linked to an abrupt switch of the cellular metabolism: a distinct stage in developmental processes of embryonic cortex or pubertal testis may require circRNAs. In these circumstances the number of circRNAs would be more important than their individual characteristics, which would be a unique feature in the transcripts world.