A high-content RNAi screen reveals multiple roles for long noncoding RNAs in cell division

Lovorka Stojic (), Aaron T. L. Lun, Patrice Mascalchi, Christina Ernst, Aisling M. Redmond, Jasmin Mangei, Alexis R. Barr, Vicky Bousgouni, Chris Bakal, John C. Marioni, Duncan T. Odom () and Fanni Gergely ()
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Lovorka Stojic: University of Cambridge
Aaron T. L. Lun: University of Cambridge
Patrice Mascalchi: University of Cambridge
Christina Ernst: University of Cambridge
Aisling M. Redmond: University of Cambridge
Jasmin Mangei: University of Cambridge
Alexis R. Barr: Institute of Cancer Research
Vicky Bousgouni: Institute of Cancer Research
Chris Bakal: Institute of Cancer Research
John C. Marioni: University of Cambridge
Duncan T. Odom: University of Cambridge
Fanni Gergely: University of Cambridge

Nature Communications, 2020, vol. 11, issue 1, 1-21

Abstract: Abstract Genome stability relies on proper coordination of mitosis and cytokinesis, where dynamic microtubules capture and faithfully segregate chromosomes into daughter cells. With a high-content RNAi imaging screen targeting more than 2,000 human lncRNAs, we identify numerous lncRNAs involved in key steps of cell division such as chromosome segregation, mitotic duration and cytokinesis. Here, we provide evidence that the chromatin-associated lncRNA, linc00899, leads to robust mitotic delay upon its depletion in multiple cell types. We perform transcriptome analysis of linc00899-depleted cells and identify the neuronal microtubule-binding protein, TPPP/p25, as a target of linc00899. We further show that linc00899 binds TPPP/p25 and suppresses its transcription. In cells depleted of linc00899, upregulation of TPPP/p25 alters microtubule dynamics and delays mitosis. Overall, our comprehensive screen uncovers several lncRNAs involved in genome stability and reveals a lncRNA that controls microtubule behaviour with functional implications beyond cell division.

Date: 2020
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DOI: 10.1038/s41467-020-14978-7

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