Novel tumour suppressive protein encoded by circular RNA, circ-SHPRH, in glioblastomas.

The previously unchartered gene expression territory governed by circular RNAs is becoming clearer with the onset of deeper sequencing technologies. The translation of circular RNAs remained a controversial theory until earlier this year, when two studies [1, 2] showed endogenous circular RNA translation in vitro and in vivo, and have further provided mechanistical evidence. In this edition of Oncogene, Zhang et al., provide evidence for the first circular RNA translated with relevance to cancer; a novel tumour suppressor protein, SHPRH-146aa, produced by circ-SHPRH driven by IRES elements. The novel tumour suppressor protein produced by the circular RNA was found to work in synergy with the full-length protein, behaving as a protective decoy molecule to decrease degradation, and thus increasing the tumour suppressive functionality of the gene. An extended patient survival time was seen in glioblastoma patients with elevated levels of SHPRH-146aa. This study also marks the discovery of the first circular RNA with an overlapping initiation and termination codon, resulting in the translation of the full circRNA, exploring a mechanism not previously found or seen.