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A long nuclear-retained non-coding RNA regulates synaptogenesis by modulating gene expression

Delphine Bernard, Kannanganattu V Prasanth, Vidisha Tripathi, Sabrina Colasse, Tetsuya Nakamura, Zhenyu Xuan, Michael Q Zhang, Frédéric Sedel, Laurent Jourdren, Fanny Coulpier, Antoine Triller, David L Spector and Alain Bessis

A growing number of long nuclear-retained non-coding RNAs (ncRNAs) have recently been described. However, few functions have been elucidated for these ncRNAs. Here, we have characterized the function of one such ncRNA, identified as metastasis-associated lung adenocar- cinoma transcript 1 (Malat1). Malat1 RNA is expressed in numerous tissues and is highly abundant in neurons. It is enriched in nuclear speckles only when RNA polymerase II-dependent transcription is active. Knock-down studies revealed that Malat1 modulates the recruitment of SR family pre-mRNA-splicing factors to the transcription site of a transgene array. DNA microarray analysis in Malat1- depleted neuroblastoma cells indicates that Malat1 con- trols the expression of genes involved not only in nuclear processes, but also in synapse function. In cultured hippo- campal neurons, knock-down of Malat1 decreases synap- tic density, whereas its over-expression results in a cell- autonomous increase in synaptic density. Our results suggest that Malat1 regulates synapse formation by mod- ulating the expression of genes involved in synapse for- mation and/or maintenance.

EMBO J. 2010 Sep 15 ;29(18):3082-93.