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RNA. 2014 Dec;20(12):1844-9. doi: 10.1261/rna.047332.114. Epub 2014 Oct 14.

The long noncoding RNA Neat1 is required for mammary gland development and lactation.

Author information

1
Center for the Biology of Disease, Laboratory for Molecular Cancer Biology, VIB, Leuven 3000, Belgium Center for Human Genetics, Laboratory for Molecular Cancer Biology, KULeuven, Leuven 3000, Belgium.
2
Center for the Biology of Disease, Histopathology Lab, VIB, Leuven 3000, Belgium Center for Human Genetics, Histopathology Lab, KULeuven, Leuven 3000, Belgium.
3
Université Libre de Bruxelles, IRIBHM, Brussels 1070, Belgium.
4
Institute for Genetic Medicine, Hokkaido University, Sapporo 060-0815, Japan.
5
RNA Biology Laboratory, RIKEN, Saitama 351-0198, Japan.
6
Center for the Biology of Disease, Laboratory for Molecular Cancer Biology, VIB, Leuven 3000, Belgium Center for Human Genetics, Laboratory for Molecular Cancer Biology, KULeuven, Leuven 3000, Belgium jeanchristophe.marine@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.

KEYWORDS:

NEAT1; long noncoding RNA; mammary gland development; paraspeckles

PMID:
25316907
PMCID:
PMC4238351
DOI:
10.1261/rna.047332.114
[Indexed for MEDLINE]
Free PMC Article

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