Long non-coding RNA-derived peptides are immunogenic and drive a potent anti-tumour response

Protein arginine methyltransferase (PRMT) 5 is over-expressed in a variety of cancers and the master transcription regulator E2F1 is an important methylation target. We have explored the role of PRMT5 and E2F1 in regulating the non-coding genome and report here a striking effect on long non-coding (lnc) RNA gene expression. Moreover, many MHC class I protein-associated peptides were derived from small open reading frames in the lncRNA genes. Pharmacological inhibition of PRMT5 or adjusting E2F1 levels qualitatively altered the repertoire of lncRNA-derived peptide antigens displayed by tumour cells. When presented to the immune system as either ex vivo-loaded dendritic cells or expressed from a viral vector, lncRNA-derived peptides drove a potent antigen-specific CD8 T lymphocyte response, which translated into a significant delay in tumour growth. Thus, lncRNA genes encode immunogenic peptides that can be deployed as a cancer vaccine. Long noncoding RNA molecules are RNA transcripts long thought to remain untranslated. In this study, the authors demonstrate that certain lncRNA can be translated into peptides that are immunogenic to CD8(+) T cells and promote anti-tumour responses when delivered as vaccine vectors in mice.

Automated summary

PRMT5, an over-expressed protein arginine methyltransferase (PRMT) in various cancers, plays a role in regulating the non-coding genome by affecting long non-coding (lnc) RNA gene expression. Additionally, inhibiting PRMT5 or adjusting E2F1 levels alters the repertoire of lncRNA-derived peptide antigens displayed by tumor cells and lncRNA-derived peptides can induce a potent antigen-specific CD8 T lymphocyte response when used as a cancer vaccine.