LncSwitch – A Novel Response Mechanism To Cellular Stress Mediated By LncRNAs Localization

LncRNAs are transcripts of over 200 nucleotides in length that are not translated into proteins. Recent studies have revealed that the regulatory function of lncRNAs depends on their subcellular localization. Nevertheless, the functional role of most lncRNAs is yet to be discovered.

While, polyadenylated RNAs are exported to the cytoplasm, many lncRNAs function in dual nuclear and cytoplasmic localizations. Interestingly, for several lncRNAs, it was demonstrated that the nuclear and cytoplasmatic fractions could interact with different partners and even have opposite functions. Moreover, some lncRNAs migrate and change localization in response to changes in biological conditions such as stress.

To study the role of subcellular localization of lncRNAs in the DDR, I exposed cells to ionizing radiation, followed by cell fractionation and RNA extraction. Next, I compared the transcriptome of the different fractions using next-generation sequencing. When comparing irradiated and control cells, our analysis identified about 800 and 1000 genes (both coding and non-coding) differentially expressed between the nucleus and the cytoplasm, respectively. Interestingly, functional gene enrichment analysis identified differences in the enriched pathways.

Focusing on lncRNAs, our results support the hypothesis that changes in their sub-cellular expression play a role in the stress response. Hence it is intriguing to hypothesize that the changes in the concentration between the fractions have a functional role in genome stability and tumorigenicity. In my study, I aim to identify and characterize these lncRNAs to unfold the mechanisms and functions of these novel genes. These findings will reveal a new role for lncRNAs, and new mechanisms for post-transcriptional regulation.