A toolkit to decipher mechanistic insights of long non-coding RNAs based on guided CRISPR screens
Long non-coding RNAs (lncRNAs) are a large and diverse group of non-protein-coding genes whose functions span a wide range of cellular processes in healthy cells and in the progression of various diseases. Despite their potential roles in many major cellular processes, the molecular function of the majority of lncRNAs remains unknown. To improve the strategy for lncRNA identification, we developed two strategies to discover novel functional lncRNAs and characterize their molecular mechanisms of action. First, we developed a machine learning called INFLAMeR to predict functional lncRNAs in a cell type-specific manner. INFLAMeR showed high predictive accuracy, and we saw that the lncRNA SNHG6 affected haematopoiesis in leukaemia cells.Second, we designed a compact CRISPRi-based screening strategy called SPPARCL to identify new lncRNAs that function in diverse cellular stresses. Through this, we saw that LINC00680 affects tRNA expression and ribosome assembly. Together, these tools offer important new ways to identify lncRNAs that function in health and disease.
