Abstract

Long noncoding RNAs (lncRNAs) regulate many biological processes and have been implicated in development and disease pathogenesis. However of 16,000 lncRNAs identified in humans only ~100 have been functionally characterised. To address whether any of these lncRNAs play a role in cell division, we performed an RNAi screen targeting 2231 human lncRNAs. High-throughput microscopy coupled with automated image analysis uncovered several lncRNAs that are required for normal cell division.

We validated and functionally characterized a number of lncRNAs. Depletion of these lncRNAs by RNAi, genome editing and antisense oligonucleotides revealed mitotic defects ranging from aberrant spindle formation, chromosome misalignment, mitotic delay and unfaithful chromosome segregation. Functional genomics combined with proteomics and cell biology will elucidate the molecular mechanisms of how these lncRNAs serve to preserve genome integrity.

Authors:

Lovorka Stojic 1, Patrice Mascalchi 1, Aaron Lun 1, Jasmin Mangei 1, Alexis Barr 2, Jeremy Pike 1, Chris Bakal 2, John Marioni 1, Duncan T Odom 1, Fanni Gergely 1.

1 University of Cambridge, CRUK Cambridge Institute, Cambridge, UK. 2 The Institute of Cancer Research, London, UK.