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

Ryu Miyagawa, Keiko Tano, R. I.E. Mizuno, Y. O. Nakamura, Kenichi Ijiri, Randeep Rakwal, Junko Shibato, Yoshinori Masuo, Akila Mayeda, Tetsuro Hirose, Nobuyoshi Akimitsu

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119 Citations (Scopus)

Abstract

MALAT-1 noncoding RNA is localized to nuclear speckles despite its mRNA-like characteristics. Here, we report the identification of several key factors that promote the localization of MALAT-1 to nuclear speckles and also 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. RNAi-mediated repression of the nuclear speckle proteins, RNPS1, SRm160, or IBP160, which are well-known mRNA processing factors, resulted in the diffusion of MALAT-1 to the nucleoplasm. We demonstrated that MALAT-1 contains two distinct elements directing transcripts to nuclear speckles, which were also capable of binding to RNPS1 in vitro. Depletion of MALAT-1 represses the expression of several genes. Taken together, our results suggest that RNPS1, SRm160, and IBP160 contribute to the localization of MALAT-1 to nuclear speckles, where MALAT-1 could be involved in regulating gene expression.

Original languageEnglish
Pages (from-to)738-751
Number of pages14
JournalRNA
Volume18
Issue number4
DOIs
Publication statusPublished - 01-04-2012

All Science Journal Classification (ASJC) codes

  • Molecular Biology

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    Miyagawa, R., Tano, K., Mizuno, R. I. E., Nakamura, Y. O., Ijiri, K., Rakwal, R., Shibato, J., Masuo, Y., Mayeda, A., Hirose, T., & Akimitsu, N. (2012). Identification of cis- and trans-acting factors involved in the localization of MALAT-1 noncoding RNA to nuclear speckles. RNA, 18(4), 738-751. https://doi.org/10.1261/rna.028639.111