This work as first presents direct involvement of XRN1 and DIS3 in dynamic regulation of cytoplasmic lncRNAs in human cells. Cells use multiple ways to regulate levels of their RNAs. Previously used techniques required long lagging times during which cells could compensate for the lack of one protein, making impossible to evaluate the direct impact of protein of interest in the degradation of particular ncRNAs. In system applied in my study, the removal of a regulatory protein is much faster, providing more relevant information about the role of the investigated proteins. Additionally, DIS3 gene mutations were found in a fraction of patients with multiple myeloma, thus we are further exploiting relevant clinical data from our collaborator (Claudia Haferlach, MLL Münchner Leukämielabor GmbH, Munich, Germany) to see if I can find a link between patients samples with DIS3 mutation and our molecular mechanisms. Recently, a role of lncRNAs as transcripts producing peptides (a short chain of amino acids) starts to be appreciated, even though lncRNAs were thought to be non-coding. Some of this short peptides were shown to have a molecular function. Thus, some of the lncRNAs accumulating after removal of DIS3 or XRN1 could be source of such peptides and they could have some relevance for the cells. Identification of such short peptides that could have functional relevance can be a perspective study, further exploring results obtained during this MSCA fellowship. Moreover, if some of the lncRNA derived peptides would be presented on the cell surface and specific to cancer cells, they could be also explored as potential targets for immunotherapy.
