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

Area of Science:

• Molecular Biology
• Genomics
• Cancer Research

Background:

• Circular RNAs (circRNAs) were once considered non-coding, but recent studies confirm their translation capabilities.
• The functional and translational relevance of circRNAs, particularly in cancer, remains an active area of investigation.

Purpose of the Study:

• To identify and characterize the first translated circular RNA with direct relevance to cancer.
• To elucidate the mechanism of action and clinical significance of the novel protein produced by this circRNA.

Main Methods:

• Utilized deep sequencing technologies to identify novel circRNAs.
• Employed in vitro and in vivo experiments to confirm endogenous circRNA translation.
• Investigated the functional role of the novel circRNA-derived protein in cancer models.

Main Results:

• Identified circ-SHPRH as the first circular RNA translated into a cancer-relevant protein, SHPRH-146aa.
• Demonstrated that SHPRH-146aa acts as a tumor suppressor by synergizing with the full-length protein and preventing degradation.
• Observed extended survival in glioblastoma patients with higher SHPRH-146aa levels.
• Discovered a novel translation mechanism involving overlapping initiation and termination codons for the full circRNA.

Conclusions:

• Circular RNA translation is relevant to cancer, offering new therapeutic targets.
• SHPRH-146aa is a novel tumor suppressor with potential clinical applications in glioblastoma.
• The discovery of overlapping codons in circRNA translation opens new avenues for understanding gene expression.