title: Protein arginine methyltransferase CARM1 attenuates the paraspeckle-mediated nuclear retention of mRNAs containing IRAlus.
abstract: In many cells, mRNAs containing inverted repeated Alu elements (IRAlus) in their 3' untranslated regions (UTRs) are inefficiently exported to the cytoplasm. Such nuclear retention correlates with paraspeckle-associated protein complexes containing p54(nrb). However, nuclear retention of mRNAs containing IRAlus 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 IRAlus. CARM1 regulates this nuclear retention pathway at two levels: CARM1 methylates the coiled-coil domain of p54(nrb), resulting in reduced binding of p54(nrb) to mRNAs containing IRAlus, 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 IRAlus 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.
authors: State Key Laboratory of Molecular Biology, Institute of Biochemistry and Cell Biology, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai 200031, China;
authors: Shi-Bin
authors: SB
authors: Hu
authors: State Key Laboratory of Molecular Biology, Institute of Biochemistry and Cell Biology, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai 200031, China;
authors: Jian-Feng
authors: JF
authors: Xiang
authors: State Key Laboratory of Molecular Biology, Institute of Biochemistry and Cell Biology, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai 200031, China;
authors: Xiang
authors: X
authors: Li
authors: State Key Laboratory of Molecular Biology, Institute of Biochemistry and Cell Biology, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai 200031, China;
authors: Yefen
authors: Y
authors: Xu
authors: Key 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;
authors: Wei
authors: W
authors: Xue
authors: State Key Laboratory of Molecular Biology, Institute of Biochemistry and Cell Biology, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai 200031, China;
authors: Min
authors: M
authors: Huang
authors: State Key Laboratory of Molecular Biology, Institute of Biochemistry and Cell Biology, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai 200031, China;
authors: Catharine C
authors: CC
authors: Wong
authors: The University of Texas M.D. Anderson Cancer Center, Smithville, Texas 78957, USA;
authors: Cari A
authors: CA
authors: Sagum
authors: The University of Texas M.D. Anderson Cancer Center, Smithville, Texas 78957, USA;
authors: Mark T
authors: MT
authors: Bedford
authors: Key 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; School of Life Science and Technology, ShanghaiTech University, Shanghai 200031, China.
authors: Li
authors: L
authors: Yang
authors: The University of Texas M.D. Anderson Cancer Center, Smithville, Texas 78957, USA; linglingchen@sibcb.ac.cn dcheng@mdanderson.org.
authors: Donghang
authors: D
authors: Cheng
authors: State Key Laboratory of Molecular Biology, Institute of Biochemistry and Cell Biology, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai 200031, China; School of Life Science and Technology, ShanghaiTech University, Shanghai 200031, China linglingchen@sibcb.ac.cn dcheng@mdanderson.org.
authors: Ling-Ling
authors: LL
authors: Chen
mesh_terms: D020087:Alu Elements / Q000235:genetics; D000818:Animals; D002460:Cell Line; D002467:Cell Nucleus / Q000378:metabolism*; D019175:DNA Methylation; D005786:Gene Expression Regulation; D057809:HEK293 Cells; D006367:HeLa Cells; D006801:Humans; D055029:Inverted Repeat Sequences / Q000235:genetics; D051379:Mice; D011485:Protein Binding; D011499:Protein Processing, Post-Translational; D021381:Protein Transport; D011484:Protein-Arginine N-Methyltransferases / Q000378:metabolism*; D062085:RNA, Long Noncoding / Q000378:metabolism*; D012333:RNA, Messenger / Q000378:metabolism*
chemical_list: D062085:RNA, Long Noncoding; D012333:RNA, Messenger; D011484:Protein-Arginine N-Methyltransferases; C119966:coactivator-associated arginine methyltransferase 1
keywords: CARM1; NEAT1; nuclear retention; p54nrb; paraspeckles