A large shRNA library approach identifies lncRNA Ntep as an essential regulator of cell proliferation

Cell Death and Differentiation
Julia BeermannThomas Thum

Abstract

The mammalian cell cycle is a complex and tightly controlled event. Myriads of different control mechanisms are involved in its regulation. Long non-coding RNAs (lncRNA) have emerged as important regulators of many cellular processes including cellular proliferation. However, a more global and unbiased approach to identify lncRNAs with importance for cell proliferation is missing. Here, we present a lentiviral shRNA library-based approach for functional lncRNA profiling. We validated our library approach in NIH3T3 (3T3) fibroblasts by identifying lncRNAs critically involved in cell proliferation. Using stringent selection criteria we identified lncRNA NR_015491.1 out of 3842 different RNA targets represented in our library. We termed this transcript Ntep (non-coding transcript essential for proliferation), as a bona fide lncRNA essential for cell cycle progression. Inhibition of Ntep in 3T3 and primary fibroblasts prevented normal cell growth and expression of key fibroblast markers. Mechanistically, we discovered that Ntep is important to activate P53 concomitant with increased apoptosis and cell cycle blockade in late G2/M. Our findings suggest Ntep to serve as an important regulator of fibroblast proliferation and function. ...Continue Reading

References

May 8, 2004·Science·Gill BejeranoDavid Haussler
Nov 19, 2004·Nature·Michael B Kastan, Jiri Bartek
Oct 4, 2005·Proceedings of the National Academy of Sciences of the United States of America·Aravind SubramanianJill P Mesirov
Apr 5, 2007·Nature Protocols·Nicolaas A P FrankenChris van Bree
Jun 15, 2007·Toxicologic Pathology·Susan Elmore
Dec 29, 2007·The Journal of Pathology·T A Wynn
Feb 4, 2009·Nature Reviews. Genetics·Tim R MercerJohn S Mattick
Apr 25, 2009·PLoS Genetics·John S Mattick
Jul 17, 2010·Journal of Cellular Physiology·Guido KrenningRaghu Kalluri
Sep 10, 2010·Methods in Molecular Biology·Victor V SolovyevAsaf A Salamov
Jul 18, 2012·Proceedings of the American Thoracic Society·Carlo Vancheri
Sep 8, 2012·Nature·UNKNOWN ENCODE Project Consortium
Jul 25, 2013·Cellular and Molecular Life Sciences : CMLS·Masatoshi KitagawaTatsuya Ohhata
Oct 10, 2013·Nature Reviews. Molecular Cell Biology·Sarah Geisler, Jeff Coller
Jun 30, 2014·Trends in Genetics : TIG·Keith W Vance, Chris P Ponting
Jan 16, 2016·Cell Systems·Arthur LiberzonPablo Tamayo
Feb 19, 2016·Science Translational Medicine·Janika ViereckThomas Thum
Mar 19, 2016·Circulation Research·Joshua G TraversBurns C Blaxall
Nov 9, 2016·Circulation·Christian BärThomas Thum

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Citations

Feb 28, 2020·Circulation Research·Cheng-Kai HuangThomas Thum
Jun 13, 2019·Nature Reviews. Cardiology·Dongchao Lu, Thomas Thum
Oct 22, 2018·BMC Cardiovascular Disorders·Tarun PantZhi-Dong Ge
Jul 23, 2020·Acta Pharmacologica Sinica·Xin ZhangQi-Zhu Tang
Feb 17, 2021·Cell Death & Disease·Yulia RybakovaDaniel G Anderson
Mar 10, 2021·Trends in Genetics : TIG·Giulia Guiducci, Lovorka Stojic
Mar 30, 2021·Frontiers in Physiology·Magda CorreiaSandrina Nóbrega-Pereira
Sep 18, 2021·Mammalian Genome : Official Journal of the International Mammalian Genome Society·Carlos Pulido-Quetglas, Rory Johnson

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Datasets Mentioned

BETA
GSE94049

Methods Mentioned

BETA
fluorescence-activated cell sorting
PCR
electrophoresis
transfection
biosensors
FACS
transgenic
ELISA
Flow Cytometry
X-ray

Software Mentioned

ORF Finder Calculator
Ensemble
Ensembl
elements BR
NIS
GapmeR
GraphPad Prism
BLAST
Cellecta
ImageJ

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