Regulatory RNA at the forefront of cancer research

ncRNAs are RNA molecules that unlike messenger RNAs do not code for proteins. They are implicated in transcription, and seem to affect the stability of messenger RNAs and their translation into proteins.

Recent evidence underscores the role of ncRNAs in normal development as well as various pathological conditions including cancer. A subclass of these molecules, known as long non-coding RNAs (lncRNAs), modulates transcriptional activity by binding to chromatin-modifying factors at target genes. Some of these are overexpressed in several cancers and play roles in epigenetic gene regulation during carcinogenesis.

Scientists on the EU-funded CHR_LNCRNA (Identification and functional characterization of lncRNA-chromatin protein complexes associated with specific chromatin modifications in breast cancer) project set out to investigate the role of lncRNAs in breast cancer. For this purpose, they developed a specific methodology that allowed them to identify chromatin factors that bind to RNA molecules. The photoactivatable RNA crosslinking and pulldown (PAR-CLPD) method involves crosslinking of RNA and proteins, the labelling of proteins and subsequent analysis by mass spectrometry.

CHR_LNCRNA researchers focused on lncRNAs associated with cancer-related histone modifications in normal and cancer cells. They obtained more than ten novel RNA-binding chromatin protein candidates that specifically bound to methylated lysine 9 residue of histone H3. Identification of these proteins will help comprehend the mode of action of lncRNAs and identify putative therapeutic targets.

The CHR_LNCRNA-developed methodology should undoubtedly fuel future basic and clinical research into the role of lncRNAs in health and disease. Long-term the outcome of such studies has the potential to translate into novel anti-cancer therapies.