The long non-coding RNA LINC00152 is essential for cell cycle progression through mitosis in HeLa cells

Abstract In recent years, long non-coding RNA (lncRNA) research has identified essential roles of these transcripts in virtually all physiological cellular processes including tumorigenesis, but their functions and molecular mechanisms are poorly understood. In this study, we performed a high-throug...

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Main Authors: Linda Nötzold, Lukas Frank, Minakshi Gandhi, Maria Polycarpou-Schwarz, Matthias Groß, Manuel Gunkel, Nina Beil, Holger Erfle, Nathalie Harder, Karl Rohr, Jakob Trendel, Jeroen Krijgsveld, Thomas Longerich, Peter Schirmacher, Michael Boutros, Sylvia Erhardt, Sven Diederichs
Format: Article
Language:English
Published: Nature Portfolio 2017-05-01
Series:Scientific Reports
Online Access:https://doi.org/10.1038/s41598-017-02357-0
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author Linda Nötzold
Lukas Frank
Minakshi Gandhi
Maria Polycarpou-Schwarz
Matthias Groß
Manuel Gunkel
Nina Beil
Holger Erfle
Nathalie Harder
Karl Rohr
Jakob Trendel
Jeroen Krijgsveld
Thomas Longerich
Peter Schirmacher
Michael Boutros
Sylvia Erhardt
Sven Diederichs
author_facet Linda Nötzold
Lukas Frank
Minakshi Gandhi
Maria Polycarpou-Schwarz
Matthias Groß
Manuel Gunkel
Nina Beil
Holger Erfle
Nathalie Harder
Karl Rohr
Jakob Trendel
Jeroen Krijgsveld
Thomas Longerich
Peter Schirmacher
Michael Boutros
Sylvia Erhardt
Sven Diederichs
author_sort Linda Nötzold
collection DOAJ
description Abstract In recent years, long non-coding RNA (lncRNA) research has identified essential roles of these transcripts in virtually all physiological cellular processes including tumorigenesis, but their functions and molecular mechanisms are poorly understood. In this study, we performed a high-throughput siRNA screen targeting 638 lncRNAs deregulated in cancer entities to analyse their impact on cell division by using time-lapse microscopy. We identified 26 lncRNAs affecting cell morphology and cell cycle including LINC00152. This transcript was ubiquitously expressed in many human cell lines and its RNA levels were significantly upregulated in lung, liver and breast cancer tissues. A comprehensive sequence analysis of LINC00152 revealed a highly similar paralog annotated as MIR4435-2HG and several splice variants of both transcripts. The shortest and most abundant isoform preferentially localized to the cytoplasm. Cells depleted of LINC00152 arrested in prometaphase of mitosis and showed reduced cell viability. In RNA affinity purification (RAP) studies, LINC00152 interacted with a network of proteins that were associated with M phase of the cell cycle. In summary, we provide new insights into the properties and biological function of LINC00152 suggesting that this transcript is crucial for cell cycle progression through mitosis and thus, could act as a non-coding oncogene.
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spelling doaj.art-0128d3ba3b3d4231913c4de6607365c42022-12-21T20:34:09ZengNature PortfolioScientific Reports2045-23222017-05-017111310.1038/s41598-017-02357-0The long non-coding RNA LINC00152 is essential for cell cycle progression through mitosis in HeLa cellsLinda Nötzold0Lukas Frank1Minakshi Gandhi2Maria Polycarpou-Schwarz3Matthias Groß4Manuel Gunkel5Nina Beil6Holger Erfle7Nathalie Harder8Karl Rohr9Jakob Trendel10Jeroen Krijgsveld11Thomas Longerich12Peter Schirmacher13Michael Boutros14Sylvia Erhardt15Sven Diederichs16Division of RNA Biology & Cancer, German Cancer Research Center (DKFZ)Division of RNA Biology & Cancer, German Cancer Research Center (DKFZ)Division of RNA Biology & Cancer, German Cancer Research Center (DKFZ)Division of RNA Biology & Cancer, German Cancer Research Center (DKFZ)Division of RNA Biology & Cancer, German Cancer Research Center (DKFZ)ViroQuant-CellNetworks RNAi Screening Facility, BioQuant Center, Heidelberg UniversityViroQuant-CellNetworks RNAi Screening Facility, BioQuant Center, Heidelberg UniversityViroQuant-CellNetworks RNAi Screening Facility, BioQuant Center, Heidelberg UniversityDepartment of Bioinformatics and Functional Genomics, Biomedical Computer Vision Group, Heidelberg University, BioQuant, IPMB, and German Cancer Research Center (DKFZ)Department of Bioinformatics and Functional Genomics, Biomedical Computer Vision Group, Heidelberg University, BioQuant, IPMB, and German Cancer Research Center (DKFZ)German Cancer Research Center (DKFZ), Excellence Cluster CellNetworks, Heidelberg UniversityGerman Cancer Research Center (DKFZ), Excellence Cluster CellNetworks, Heidelberg UniversityInstitute of Pathology University Hospital RWTH AachenInstitute of Pathology, University Hospital HeidelbergDivision of Signaling and Functional Genomics, German Cancer Research Center (DKFZ) and Department of Cell and Molecular Biology, Medical Faculty Mannheim, Heidelberg UniversityCenter for Molecular Biology (ZMBH), DKFZ-ZMBH Alliance and CellNetworks Excellence Cluster, Heidelberg UniversityDivision of RNA Biology & Cancer, German Cancer Research Center (DKFZ)Abstract In recent years, long non-coding RNA (lncRNA) research has identified essential roles of these transcripts in virtually all physiological cellular processes including tumorigenesis, but their functions and molecular mechanisms are poorly understood. In this study, we performed a high-throughput siRNA screen targeting 638 lncRNAs deregulated in cancer entities to analyse their impact on cell division by using time-lapse microscopy. We identified 26 lncRNAs affecting cell morphology and cell cycle including LINC00152. This transcript was ubiquitously expressed in many human cell lines and its RNA levels were significantly upregulated in lung, liver and breast cancer tissues. A comprehensive sequence analysis of LINC00152 revealed a highly similar paralog annotated as MIR4435-2HG and several splice variants of both transcripts. The shortest and most abundant isoform preferentially localized to the cytoplasm. Cells depleted of LINC00152 arrested in prometaphase of mitosis and showed reduced cell viability. In RNA affinity purification (RAP) studies, LINC00152 interacted with a network of proteins that were associated with M phase of the cell cycle. In summary, we provide new insights into the properties and biological function of LINC00152 suggesting that this transcript is crucial for cell cycle progression through mitosis and thus, could act as a non-coding oncogene.https://doi.org/10.1038/s41598-017-02357-0
spellingShingle Linda Nötzold
Lukas Frank
Minakshi Gandhi
Maria Polycarpou-Schwarz
Matthias Groß
Manuel Gunkel
Nina Beil
Holger Erfle
Nathalie Harder
Karl Rohr
Jakob Trendel
Jeroen Krijgsveld
Thomas Longerich
Peter Schirmacher
Michael Boutros
Sylvia Erhardt
Sven Diederichs
The long non-coding RNA LINC00152 is essential for cell cycle progression through mitosis in HeLa cells
Scientific Reports
title The long non-coding RNA LINC00152 is essential for cell cycle progression through mitosis in HeLa cells
title_full The long non-coding RNA LINC00152 is essential for cell cycle progression through mitosis in HeLa cells
title_fullStr The long non-coding RNA LINC00152 is essential for cell cycle progression through mitosis in HeLa cells
title_full_unstemmed The long non-coding RNA LINC00152 is essential for cell cycle progression through mitosis in HeLa cells
title_short The long non-coding RNA LINC00152 is essential for cell cycle progression through mitosis in HeLa cells
title_sort long non coding rna linc00152 is essential for cell cycle progression through mitosis in hela cells
url https://doi.org/10.1038/s41598-017-02357-0
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