Modulation of the repressive capacity of the Pumilio proteins by a long noncoding RNA

The number of known long noncoding RNA (lncRNA) functions is rapidly growing, but how those functions are encoded in their sequence and structure remains poorly understood. An emerging theme is that lncRNAs can orchestrate cellular processes by nucleation of membraneless comartments. As a model for a post-transcriptional functions of a cytoplasmic noncodig RNA, we have recently characterized and been studying NORAD (noncoding RNA activated by DNA damage), an abundant, and highly conserved lncRNA that is required for proper mitotic divisions in human cells. NORAD acts in the cytoplasm and antagonizes repressors from the Pumilio family that bind at least 17 sites spread through 12 repetitive units in NORAD sequence. I will describe our studies aimed at mapping the contribution of different sequences in NORAD to its function, and the mechanism of action through which a lncRNA can tune the ability of abundant repressor molecules, the Pumilio proteins, to identify and repress their targets, and how this functionality changes as the cells traverse through the cell cyle.