The lncRNA Neat1 is required for corpus luteum formation and the establishment of pregnancy in a subpopulation of mice

Abstract

Neat1 is a non-protein-coding RNA that serves as an architectural component of the nuclear bodies known as paraspeckles. Although cell-based studies indicate that Neat1 is a crucial regulator of gene expression, its physiological relevance remains unclear. Here, we find that Neat1 knockout (KO) mice stochastically fail to become pregnant despite normal ovulation. Unilateral transplantation of wild-type ovaries or the administration of progesterone partially rescued the phenotype, suggesting that corpus luteum dysfunction and concomitant low progesterone were the primary causes of the decreased fertility. In contrast to the faint expression observed in most of the adult tissues, Neat1 was highly expressed in the corpus luteum, and the formation of luteal tissue was severely impaired in nearly half of the Neat1 KO mice. These observations suggest that Neat1 is essential for the formation of the corpus luteum and for the subsequent establishment of pregnancy under a suboptimal condition that has not yet been identified.

Architectural RNAs (arcRNAs): A class of long noncoding RNAs that function as the scaffold of nuclear bodies

“…For instance, NEAT1 is transcriptionally upregulated upon cellular stresses by viral infection or MG132 treatment [23,24]. NEAT1 is also upregulated during corpus luteum formation and mammary gland development and in disease conditions such as in motor neurons at the early stage of amyotrophic lateral sclerosis, in the brains of frontotemporal lobar degeneration patients, and in prostate and breast cancers [25][26][27][28][29]. Expression of IGS lncRNAs is induced by stresses such as heat shock and acidosis [10].…”

SWI/SNF chromatin-remodeling complexes function in noncoding RNA-dependent assembly of nuclear bodies

“…Paraspeckles are ∼360 nm in diameter (8); hence, they are considered huge among RNP particles. Paraspeckles regulate the expression of a number of genes via the sequestration of specific proteins and RNAs (4,9,10), and are physiologically involved in the development of the corpus luteum and the mammary gland in mice (11,12).…”

Long non-coding RNAs: new players in mammalian female gametogenesis

“…NEAT1 was found exclusively localized to paraspeckles and is a core component of these nuclear bodies involved in the nuclear retention of specific mRNAs (29). Moreover, NEAT1 seems to be essential for the formation of the corpus luteum and the establishment of pregnancy in mice, although its precise molecular mechanism remains to be investigated (30). Recently, increased levels of NEAT1 were found associated with placental dysfunction in idiopathic intrauterine Growth Restriction (IUGR) fetuses (31).…”