Protein arginine methyltransferase CARM1 attenuates the paraspeckle-mediated nuclear retention of mRNAs containing IRAlus (original) (raw)
- Jian-Feng Xiang1,
- Xiang Li1,
- Yefen Xu1,
- Wei Xue2,
- Min Huang1,
- Catharine C. Wong1,
- Cari A. Sagum3,
- Mark T. Bedford3,
- Li Yang2,4,
- Donghang Cheng3 and
- Ling-Ling Chen1,4
- 1State Key Laboratory of Molecular Biology, Institute of Biochemistry and Cell Biology, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai 200031, China;
- 2Key Laboratory of Computational Biology, Chinese Academy of Sciences (CAS)-German Max Planck Society (MPG) Partner Institute for Computational Biology, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai 200031, China;
- 3The University of Texas M.D. Anderson Cancer Center, Smithville, Texas 78957, USA;
- 4School of Life Science and Technology, ShanghaiTech University, Shanghai 200031, China
- Corresponding authors: linglingchen{at}sibcb.ac.cn, dcheng{at}mdanderson.org
Abstract
In many cells, mRNAs containing inverted repeated Alu elements (IR_Alu_s) in their 3′ untranslated regions (UTRs) are inefficiently exported to the cytoplasm. Such nuclear retention correlates with paraspeckle-associated protein complexes containing p54nrb. However, nuclear retention of mRNAs containing IR_Alu_s is variable, and how regulation of retention and export is achieved is poorly understood. Here we show one mechanism of such regulation via the arginine methyltransferase CARM1 (coactivator-associated arginine methyltransferase 1). We demonstrate that disruption of CARM1 enhances the nuclear retention of mRNAs containing IR_Alu_s. CARM1 regulates this nuclear retention pathway at two levels: CARM1 methylates the coiled-coil domain of p54nrb, resulting in reduced binding of p54nrb to mRNAs containing IR_Alu_s, and also acts as a transcription regulator to suppress NEAT1 transcription, leading to reduced paraspeckle formation. These actions of CARM1 work together synergistically to regulate the export of transcripts containing IR_Alu_s from paraspeckles under certain cellular stresses, such as poly(I:C) treatment. This work demonstrates how a post-translational modification of an RNA-binding protein affects protein–RNA interaction and also uncovers a mechanism of transcriptional regulation of the long noncoding RNA NEAT1.
Footnotes
Supplemental material is available for this article.
Article is online at http://www.genesdev.org/cgi/doi/10.1101/gad.257048.114.
Received December 8, 2014.
Accepted February 13, 2015.
© 2015 Hu et al.; Published by Cold Spring Harbor Laboratory Press
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