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Identification of cis- and trans-acting factors involved in the localization of MALAT-1 to nuclear speckles

ABSTRACT: MALAT-1 is a long mammalian non-coding transcript of approximately 8500 nucleotides. It is localized to nuclear speckles despite its mRNA-like characteristics, which usually result in the export of transcripts to the cytoplasm. In the present study, we report the identification of several factors that influence the nuclear speckle localization of MALAT-1, and we provide evidence that MALAT-1 is involved in the regulation of gene expression. Heterokaryon assays revealed that MALAT-1 does not shuttle between the nucleus and cytoplasm, but is stably retained within the nucleus. Analysis of MALAT-1 fragments showed that MALAT-1 contains two distinct nuclear speckle-directing elements (between nucleotides 1961 to 3040 and 6008 to 7011 of the MALAT-1 sequence). The knockdown of the nuclear speckle proteins, RNPS1, SRm160 or IBP160, resulted in the diffusion of MALAT-1 to the nucleoplasm. In addition, we have demonstrated that depletion of MALAT-1 represses the expression of several genes. This repression of gene expression also occurs in response to the delocalization of MALAT-1 from the nuclear speckles. These results suggest that RNPS1, SRm160 and IBP160 contribute to the localization of MALAT-1 to nuclear speckles where it is involved in regulating gene expression

ORGANISM(S): Homo sapiens

PROVIDER: GSE20506 | GEO | 2010/06/02

SECONDARY ACCESSION(S): PRJNA125093

REPOSITORIES: GEO

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Genome organization around nuclear speckles drives mRNA splicing efficiency

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TAF2 condensation in nuclear speckles links basal transcription factor TFIID to RNA splicing

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2024-04-26 | PXD049117 | Pride

Homo sapiens

Project description:Identification of cis- and trans-acting factors involved in the localization of MALAT-1 to nuclear speckles

| PRJNA125093 | ENA

The MALAT-1 noncoding RNA Regulates Cell Mobility by Modulating Gene Expressions

Project description:MALAT-1, originally identified as a metastasis associated long noncoding transcript in lung adenocarcinoma, is localized to nuclear speckles. However, functional role of MALAT-1 in metastatic characters in cancer cells has not been elucidated. Our current research has revealed that suppression of MALAT-1 expression in lung adenocarcinoma cell line by RNA interference significantly inhibited cellular mobility both in wound healing assay and in migration assay using Boyden's chamber. Moreover, we have identified metastasis/mobility-associated genes among down-regulated genes in the MALAT-1 knockdown cells by DNA microarray analysis. Quantitative analysis of pre-mRNAs has shown that the pre-mRNAs of some genes were suppressed in MALAT-1 knockdown cells but the others were not suppressed even though their matured mRNAs were found to be down-regulated. Our results suggest that MALAT-1 facilitates cell mobility by modulating the expression of metastasis/mobility-associated genes at the transcriptional and post-transcriptional stages.

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