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PMID: 20729808 Published · ppublish English Journal Article Research Support, N.I.H., Extramural Research Support, Non-U.S. Gov't

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

The EMBO journal ·Vol. 29 ·No. 18 ·2010-09-15 ·Pages 3082-93

Bernard D, Prasanth KV, Tripathi V, Colasse S, Nakamura T, Xuan Z, Zhang MQ, Sedel F, Jourdren L, Coulpier F, Triller A, Spector DL, Bessis A

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.

MeSH Terms
Animals Biomarkers/metabolism Blotting, Northern Bone Neoplasms/genetics,metabolism,pathology Cell Nucleus/genetics,metabolism Cells, Cultured Gene Expression Profiling Gene Expression Regulation/physiology Hippocampus/cytology,metabolism Humans Mice Neuroblastoma/genetics,metabolism,pathology Neurogenesis/physiology Neurons/cytology,metabolism Oligonucleotide Array Sequence Analysis Osteosarcoma/genetics,metabolism,pathology RNA Precursors/genetics RNA Splicing/genetics RNA, Messenger/genetics RNA, Nuclear/physiology Repressor Proteins Reverse Transcriptase Polymerase Chain Reaction Synapses/genetics Trans-Activators Transcription Factors/genetics,metabolism
Chemicals
Biomarkers Mta1 protein, mouse RNA Precursors RNA, Messenger RNA, Nuclear Repressor Proteins Trans-Activators Transcription Factors
Authors & Affiliations
13 authors, click to expand affiliations / ORCID
Bernard Delphine
Laboratoire de Biologie Cellulaire de la Synapse, Inserm 1024/CNRS 8197, Institut de Biologie de l'Ecole Normale Supérieure, Paris, France.
Prasanth Kannanganattu V
Tripathi Vidisha
Colasse Sabrina
Nakamura Tetsuya
Xuan Zhenyu
Zhang Michael Q
Sedel Frédéric
Jourdren Laurent
Coulpier Fanny
Triller Antoine
Spector David L
Bessis Alain
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Article Info
Journal
The EMBO journal
Abbr.
EMBO J
ISSN
1460-2075
DOI
10.1038/emboj.2010.199
Published
2010-09-15
Epub
2010-00-20
Pages
3082-93
Language
English
Region
England
NLM ID
8208664
PMCID
PMC2944070
Subset
IM
Grants
NCI NIH HHS · P01 CA013106 · United States
NIGMS NIH HHS · R01 GM042694 · United States
PHS HHS · 42694 · United States
NCI NIH HHS · 5P01CA013106-38 · United States
External Links
PubMed source DOI: 10.1038/emboj.2010.199 PMC Full Text View journal details
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