Journal Article

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

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

2010

Overview

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. Malat1 is a long non‐coding RNA that localizes to nuclear speckles, but whose function remains unclear. Here, the Spector and Bessis laboratories show that Malat1 is important for the recruitment of splicing factors to transcription sites, the expression of synaptic genes and as a consequence synaptogenesis.

• Publisher: John Wiley & Sons, Ltd,Nature Publishing Group UK,Springer Nature B.V,EMBO Press,Nature Publishing Group
• Subject: Animals / Biochemistry, Molecular Biology / Biomarkers - metabolism / Blotting, Northern / Bone Neoplasms - genetics / Bone Neoplasms - metabolism / Bone Neoplasms - pathology / Cell Nucleus - genetics / Cell Nucleus - metabolism / Cells, Cultured / Cellular biology / Deoxyribonucleic acid / DNA / EMBO27 / EMBO36 / Gene expression / Gene Expression Profiling / Gene Expression Regulation - physiology / Genomics / Hippocampus - cytology / Hippocampus - metabolism / Humans / Life Sciences / Mice / Molecular biology / Neuroblastoma - genetics / Neuroblastoma - metabolism / Neuroblastoma - pathology / Neurogenesis - physiology / Neurons / Neurons - cytology / Neurons - metabolism / Neurosciences / non-coding RNA / nuclear domains / Oligonucleotide Array Sequence Analysis / Osteosarcoma - genetics / Osteosarcoma - metabolism / Osteosarcoma - pathology / Reverse Transcriptase Polymerase Chain Reaction / RNA polymerase / RNA Precursors - genetics / RNA Splicing - genetics / RNA, Messenger - genetics / RNA, Nuclear - physiology / splicing factor / Synapses - genetics / synaptogenesis / transcription / Transcription Factors - genetics / Transcription Factors - metabolism