A long nuclear-retained non-coding RNA regulates synaptogenesis by modulating gene expression.
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.
Bernard
Delphine
D
Laboratoire de Biologie Cellulaire de la Synapse, Inserm 1024/CNRS 8197, Institut de Biologie de l'Ecole Normale Supérieure, Paris, France.
Prasanth
Kannanganattu V
KV
Tripathi
Vidisha
V
Colasse
Sabrina
S
Nakamura
Tetsuya
T
Xuan
Zhenyu
Z
Zhang
Michael Q
MQ
Sedel
Frédéric
F
Jourdren
Laurent
L
Coulpier
Fanny
F
Triller
Antoine
A
Spector
David L
DL
Bessis
Alain
A
D000818:Animals; D015415:Biomarkers / Q000378:metabolism*; D015152:Blotting, Northern; D001859:Bone Neoplasms / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D002467:Cell Nucleus / Q000235:genetics* / Q000378:metabolism; D002478:Cells, Cultured; D020869:Gene Expression Profiling; D005786:Gene Expression Regulation / Q000502:physiology*; D006624:Hippocampus / Q000166:cytology / Q000378:metabolism; D006801:Humans; D051379:Mice; D009447:Neuroblastoma / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D055495:Neurogenesis / Q000502:physiology*; D009474:Neurons / Q000166:cytology / Q000378:metabolism; D020411:Oligonucleotide Array Sequence Analysis; D012516:Osteosarcoma / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D012322:RNA Precursors / Q000235:genetics; D012326:RNA Splicing / Q000235:genetics; D012333:RNA, Messenger / Q000235:genetics; D015138:RNA, Nuclear / Q000502:physiology*; D012097:Repressor Proteins; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013569:Synapses / Q000235:genetics*; D015534:Trans-Activators; D014157:Transcription Factors / Q000235:genetics* / Q000378:metabolism
D015415:Biomarkers; C503336:Mta1 protein, mouse; D012322:RNA Precursors; D012333:RNA, Messenger; D015138:RNA, Nuclear; D012097:Repressor Proteins; D015534:Trans-Activators; D014157:Transcription Factors