PT  - JOURNAL ARTICLE
AU  - Carmen Adriaens
AU  - Florian Rambow
AU  - Greet Bervoets
AU  - Toomas Silla
AU  - Mari Mito
AU  - Tomoki Chiba
AU  - Asahara Hiroshi
AU  - Tetsuro Hirose
AU  - Shinichi Nakagawa
AU  - Torben Heick Jensen
AU  - Jean-Christophe Marine
TI  - The lncRNA <em>NEAT1_1</em> is dispensable for normal tissue homeostasis and cancer cell growth
AID  - 10.1101/574582
DP  - 2019 Jan 01
TA  - bioRxiv
PG  - 574582
4099  - http://biorxiv.org/content/early/2019/03/18/574582.short
4100  - http://biorxiv.org/content/early/2019/03/18/574582.full
AB  - NEAT1 is one of the most studied lncRNAs, in part because its silencing in mice causes defects in mammary gland development and corpus luteum formation, and protects them from skin cancer development. Moreover, depleting NEAT1 in established cancer cell lines reduces growth and sensitizes cells to DNA damaging agents. However, NEAT1 produces two isoforms and because the short isoform, NEAT1_1, completely overlaps the 5’ part of the long NEAT1_2 isoform, the respective contributions of each of the isoforms to these phenotypes has remained unclear. Whereas NEAT1_1 is highly expressed in most tissues, NEAT1_2 is the central architectural component of paraspeckles, which are nuclear bodies that assemble in specific tissues and cells exposed to various forms of stress. Using dual RNA-FISH to detect both NEAT1_1 outside of paraspeckles and NEAT1_2/NEAT1 inside this nuclear body, we report herein that NEAT1_1 levels are dynamically regulated during the cell cycle and targeted for degradation by the nuclear RNA exosome. Unexpectedly, however, cancer cells engineered to lack NEAT1_1, but not NEAT1_2, do not exhibit cell cycle defects. Moreover, Neat1_1-specific knockout mice do not exhibit the phenotypes observed in Neat1-deficient mice. We propose that NEAT1 functions are mainly, if not exclusively, attributable to NEAT1_2 and, by extension, to paraspeckles. Graphical abstract