RT Journal Article
SR Electronic
T1 A high-content RNAi screen reveals multiple roles for long noncoding RNAs in cell division
JF bioRxiv
FD Cold Spring Harbor Laboratory
SP 709030
DO 10.1101/709030
A1 Lovorka Stojic
A1 Aaron T L Lun
A1 Patrice Mascalchi
A1 Christina Ernst
A1 Aisling M Redmond
A1 Jasmin Mangei
A1 Alexis R Barr
A1 Vicky Bousgouni
A1 Chris Bakal
A1 John C Marioni
A1 Duncan T Odom
A1 Fanni Gergely
YR 2019
UL http://biorxiv.org/content/early/2019/07/19/709030.abstract
AB Genome stability relies on proper coordination of mitosis and cytokinesis, where dynamic microtubules capture and faithfully segregate chromosomes into daughter cells. The role of long noncoding RNAs (lncRNAs) in controlling these processes however remains largely unexplored. To identify lncRNAs with mitotic functions, we performed a high-content RNAi imaging screen targeting more than 2,000 human lncRNAs. By investigating major hallmarks of cell division such as chromosome segregation, mitotic duration and cytokinesis, we discovered numerous lncRNAs with functions in each of these processes. The chromatin-associated lncRNA, linc00899, was selected for in-depth studies due to the robust mitotic delay observed upon its depletion. Transcriptome analysis of linc00899-depleted cells together with gain-of-function and rescue experiments across multiple cell types identified the neuronal microtubule-binding protein, TPPP/p25, as a target of linc00899. Linc00899 binds the genomic locus of TPPP/p25 and suppresses its transcription through a cis-acting mechanism. In cells depleted of linc00899, the consequent upregulation of TPPP/p25 alters microtubule dynamics and is necessary and sufficient to delay mitosis. Overall, our comprehensive screen identified several lncRNAs with roles in genome stability and revealed a new lncRNA that controls microtubule behaviour with functional implications beyond cell division.