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, Alain Bessis

Research output: Contribution to journalArticlepeer-review

596 Scopus citations

Abstract

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 adenocarcinoma 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 controls the expression of genes involved not only in nuclear processes, but also in synapse function. In cultured hippocampal neurons, knock-down of Malat1 decreases synaptic density, whereas its over-expression results in a cell-autonomous increase in synaptic density. Our results suggest that Malat1 regulates synapse formation by modulating the expression of genes involved in synapse formation and/or maintenance.

Original languageEnglish (US)
Pages (from-to)3082-3093
Number of pages12
JournalEMBO Journal
Volume29
Issue number18
DOIs
StatePublished - Sep 2010
Externally publishedYes

Keywords

  • non-coding RNA
  • nuclear domains
  • splicing factor
  • synaptogenesis
  • transcription

ASJC Scopus subject areas

  • General Neuroscience
  • Molecular Biology
  • General Biochemistry, Genetics and Molecular Biology
  • General Immunology and Microbiology

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