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

Published version
Peer-reviewed

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Authors

Mascalchi, Patrice 
Ernst, Christina 
Redmond, Aisling M.  ORCID logo  https://orcid.org/0000-0001-9070-1780

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.

Description

Keywords

Article, /631/1647/2163, /631/208/200, /631/337/641/1655, /631/337/384/2568, /14, /14/32, /14/63, /38, /38/89, /38/91, /49, /13, article

Journal Title

Nature Communications

Conference Name

Journal ISSN

2041-1723

Volume Title

11

Publisher

Nature Publishing Group UK
Sponsorship
Cancer Research UK (CRUK) (C14303/A17197, A20412)