Long Non-Coding RNA and Alternative Splicing Modulations in Parkinson's Leukocytes Identified by RNA Sequencing

Long non-coding RNAs (lncRNAs) comprise a novel, fascinating class of RNAs with largely unknown biological functions. Parkinson’s-disease (PD) is the most frequent motor disorder, and Deep-brain-stimulation (DBS) treatment alleviates the symptoms, but early disease biomarkers are still unknown and new future genetic interference targets are urgently needed.

Using RNA-sequencing technology and a novel computational workflow for in-depth exploration of whole-transcriptome RNA-seq datasets, a team led by researchers at the Hebrew University-Hadassah Medical School detected and analyzed lncRNAs in sequenced libraries from PD patients’ leukocytes pre and post-treatment and the brain, adding this full profile resource of over 7,000 lncRNAs to the few human tissues-derived lncRNA datasets that are currently available. Their study includes sample-specific database construction, detecting disease-derived changes in known and novel lncRNAs, exons and junctions and predicting corresponding changes in Polyadenylation choices, protein domains and miRNA binding sites. They report widespread transcript structure variations at the splice junction and exons levels, including novel exons and junctions and alteration of lncRNAs followed by experimental validation in PD leukocytes and two PD brain regions compared with controls. These results suggest lncRNAs involvement in neurodegenerative diseases, and specifically PD. This comprehensive workflow will be of use to the increasing number of laboratories producing RNA-Seq data in a wide range of biomedical studies.

• Soreq L, Guffanti A, Salomonis N, Simchovitz A, Israel Z, et al. (2014) Long Non-Coding RNA and Alternative Splicing Modulations in Parkinson’s Leukocytes Identified by RNA Sequencing. PLoS Comput Biol 10(3): e1003517. [article]