title: Loss of the abundant nuclear non-coding RNA MALAT1 is compatible with life and development.
abstract: The metastasis-associated lung adenocarcinoma transcript 1, MALAT1, is a long non-coding RNA (lncRNA) that has been discovered as a marker for lung cancer metastasis. It is highly abundant, its expression is strongly regulated in many tumor entities including lung adenocarcinoma and hepatocellular carcinoma as well as physiological processes, and it is associated with many RNA binding proteins and highly conserved throughout evolution. The nuclear transcript MALAT-1 has been functionally associated with gene regulation and alternative splicing and its regulation has been shown to impact proliferation, apoptosis, migration and invasion.       Here, we have developed a human and a mouse knockout system to study the loss-of-function phenotypes of this important ncRNA. In human tumor cells, MALAT1 expression was abrogated using Zinc Finger Nucleases. Unexpectedly, the quantitative loss of MALAT1 did neither affect proliferation nor cell cycle progression nor nuclear architecture in human lung or liver cancer cells. Moreover, genetic loss of Malat1 in a knockout mouse model did not give rise to any obvious phenotype or histological abnormalities in Malat1-null compared with wild-type animals. Thus, loss of the abundant nuclear long ncRNA MALAT1 is compatible with cell viability and normal development.
authors.affiliation: Georg-Speyer-Haus, Frankfurt, Germany.
authors.forename: Moritz
authors.initials: M
authors.lastname: Eißmann
authors.forename: Tony
authors.initials: T
authors.lastname: Gutschner
authors.forename: Monika
authors.initials: M
authors.lastname: Hämmerle
authors.forename: Stefan
authors.initials: S
authors.lastname: Günther
authors.forename: Maïwen
authors.initials: M
authors.lastname: Caudron-Herger
authors.forename: Matthias
authors.initials: M
authors.lastname: Groß
authors.forename: Peter
authors.initials: P
authors.lastname: Schirmacher
authors.forename: Karsten
authors.initials: K
authors.lastname: Rippe
authors.forename: Thomas
authors.initials: T
authors.lastname: Braun
authors.forename: Martin
authors.initials: M
authors.lastname: Zörnig
authors.forename: Sven
authors.initials: S
authors.lastname: Diederichs
mesh_terms: D000818:Animals; D002467:Cell Nucleus / Q000378:metabolism; D002470:Cell Survival; D055786:Gene Knockout Techniques; D006801:Humans; D008113:Liver Neoplasms / Q000378:metabolism / Q000473:pathology*; D008175:Lung Neoplasms / Q000378:metabolism / Q000473:pathology*; D051379:Mice; D018345:Mice, Knockout; D062085:RNA, Long Noncoding / Q000235:genetics / Q000378:metabolism*
chemical_list: C557041:MALAT1 long non-coding RNA, human; C557040:Malat1 long non-coding RNA, mouse; C577275:NEAT1 long non-coding RNA, mouse; D062085:RNA, Long Noncoding