Dataset Information

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

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.

SUBMITTER: Stojic L

PROVIDER: S-EPMC7160116 | biostudies-literature | 2020 Apr

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

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

Stojic Lovorka L Lun Aaron T L ATL Mascalchi Patrice P Ernst Christina C Redmond Aisling M AM Mangei Jasmin J Barr Alexis R AR Bousgouni Vicky V Bakal Chris C Marioni John C JC Odom Duncan T DT Gergely Fanni F

Nature communications 20200415 1

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 dep ...[more]

PMID: 32296040

Similar Datasets

Project description:AimsAnthracyclines (ANTs) are essential chemotherapeutic agents; however, their adverse effects can lead to heart failure in cancer survivors. While long non-coding RNAs (lncRNAs) have become new players in cellular processes, there is limited knowledge on lncRNA expression related to anthracyclines-induced cardiotoxicity. This study investigates the lncRNA profiles in human cardiac microtissues exposed to 3 popular ANTs, namely doxorubicin, epirubicin, and idarubicin, as well as in heart biopsies from ANT-treated patients.Methods and resultsThe in vitro microtissues were exposed to each ANT at 2 doses over 2 weeks; the transcriptome data was collected at 7 time points. The human biopsies were collected from heart failure patients who underwent ANT treatment and control subjects. Over 100 lncRNAs were differentially expressed in each in vitro ANT treatment condition compared to control samples; 16 of them were differentially expressed across all ANT-treated conditions. The lncRNA databases and literature revealed insight on how these lncRNAs relate to heart failure and cellular functions. For instance, H19 and RMRP are involved in heart failure progression, while BDNF-AS is a cardiomyocyte damage-associated gene; SNHG7 is a cardiac hypertrophy regulator. PCAT19 can promote the miR-182/PDK4 axis and modulate p53 expression, whereas SNHG29 can regulate the Wnt/β-catenin signaling pathway via the miR-223-3p/CTNND1 axis. Other lncRNAs, which were only differentially expressed in particular ANT-treated conditions, are also involved in cardiomyocyte damage and heart failure disease. The alterations of these lncRNA expressions in the in vitro cardiac tissue were also affirmed by similar changes in the human biopsies.ConclusionThis study revealed several lncRNAs that can be potential biomarkers or targets for further ANT-induced cardiotoxicity investigation, according to the transcriptome in both human cardiac microtissues expose to ANTs as well as in heart biopies form ANT-treated patients. Especially, H19 lncRNA showed its contribution to on-target toxicity, in which it is involved in both chemoresistance and cardiotoxic mechanism.

Dataset Information

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

Publications

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

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets