The long noncoding RNA Neat1 is required for mammary gland development and lactation (original) (raw)

  1. Carmen Adriaens1,2,
  2. Enrico Radaelli3,4,
  3. Alexandra Van Keymeulen5,
  4. Cedric Blanpain5,
  5. Tetsuro Hirose6,
  6. Shinichi Nakagawa7 and
  7. Jean-Christophe Marine1,2
  8. 1Center for the Biology of Disease, Laboratory for Molecular Cancer Biology, VIB, Leuven 3000, Belgium
  9. 2Center for Human Genetics, Laboratory for Molecular Cancer Biology, KULeuven, Leuven 3000, Belgium
  10. 3Center for the Biology of Disease, Histopathology Lab, VIB, Leuven 3000, Belgium
  11. 4Center for Human Genetics, Histopathology Lab, KULeuven, Leuven 3000, Belgium
  12. 5Université Libre de Bruxelles, IRIBHM, Brussels 1070, Belgium
  13. 6Institute for Genetic Medicine, Hokkaido University, Sapporo 060-0815, Japan
  14. 7RNA Biology Laboratory, RIKEN, Saitama 351-0198, Japan
  15. Corresponding author: jeanchristophe.marine{at}cme.vib-kuleuven.be

Abstract

The lncRNA Neat1 is an essential architectural component of paraspeckle nuclear bodies. Although cell-based studies identified Neat1-paraspeckles as key regulators of gene expression through retention of hyperdited mRNAs and/or transcription factors, it is unclear under which specific physiological conditions paraspeckles are formed in vivo and whether they have any biological relevance. Herein, we show that paraspeckles are assembled in luminal epithelial cells during mammary gland development. Importantly, genetic ablation of Neat1 results in aberrant mammary gland morphogenesis and lactation defects. We provide evidence that the lactation defect is caused by a decreased ability of Neat1-mutant cells to sustain high rates of proliferation during lobular-alveolar development. This study is the first to assign an important biological function to the lncRNA Neat1 and to link it to the presence of paraspeckles nuclear bodies in vivo.

Footnotes