Identification of cis- and trans-acting factors involved in the localization of MALAT-1 noncoding RNA to nuclear speckles
- Ryu Miyagawa1,
- Keiko Tano1,
- Rie Mizuno1,
- Yo Nakamura1,
- Kenichi Ijiri1,
- Randeep Rakwal2,
- Junko Shibato2,
- Yoshinori Masuo2,
- Akila Mayeda3,
- Tetsuro Hirose4 and
- Nobuyoshi Akimitsu1,5
- 1Radioisotope Center, The University of Tokyo, Bunkyo-ku, Tokyo 113-0032, Japan
- 2Health Technology Research Center, National Institute of Advanced Industrial Science and Technology (AIST) West, Tsukuba, Ibaraki 305-8569, Japan
- 3Institute for Comprehensive Medical Science (ICMS), Fujita Health University, Kutsukake-cho, Toyoake, Aichi 470-1192, Japan
- 4Functional RNomics Team, Biomedicinal Information Research Center, AIST, Tokyo 135-0064, Japan
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.
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Footnotes
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↵5 Corresponding author.
E-mail akimitsu{at}ric.u-tokyo.ac.jp.
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Article published online ahead of print. Article and publication date are at http://www.rnajournal.org/cgi/doi/10.1261/rna.028639.111.
- Received June 12, 2011.
- Accepted December 15, 2011.
- Copyright © 2012 RNA Society