The Biogenesis of Nascent Circular RNAs

Publication date: Available online 7 April 2016
Source:Cell Reports
Author(s): Yang Zhang, Wei Xue, Xiang Li, Jun Zhang, Siye Chen, Jia-Lin Zhang, Li Yang, Ling-Ling Chen
Steady-state circular RNAs (circRNAs) have been mapped to thousands of genomic loci in mammals. We studied circRNA processing using metabolic tagging of nascent RNAs with 4-thiouridine (4sU). Strikingly, the efficiency of circRNA processing from pre-mRNA is extremely low endogenously. Additional studies revealed that back-splicing outcomes correlate with fast RNA Polymerase II elongation rate and are tightly controlled by cis-elements in vivo. Additionally, prolonged 4sU labeling in cells shows that circRNAs are largely processed post-transcriptionally and that circRNAs are stable. Circular RNAs that are abundant at a steady-state level tend to accumulate. This is particularly true in cells, such as neurons, that have slow division rates. This study uncovers features of circRNA biogenesis by investigating the link between nascent circRNA processing and transcription.

Graphical abstract

Teaser

Zhang et al. study the link between circRNA processing and transcription using 4sUDRB-seq. They find that circRNA production from pre-mRNA back-splicing is slow and largely occurs post-transcriptionally. The authors argue that circRNAs that are abundant at a steady-state level tend to be transcribed quickly and accumulate.


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