title: Transcriptome-wide analysis of TDP-43 binding small RNAs identifies miR-NID1 (miR-8485), a novel miRNA that represses NRXN1 expression.
abstract: The Tar DNA-binding protein 43 (TARDBP, TDP-43) regulates RNA processing and miRNA biogenesis and is known to be involved in neurodegeneration. Messenger RNA (mRNA) targets of TDP-43 have recently been systematically identified, but small RNAs (sRNAs) bound by TDP-43 have not been studied in details. Here, we reexamine cross-linking, immunoprecipitation and sequencing (CLIP-seq) data, and identify pre-miRNAs, miRNAs and piRNAs bound by TDP-43 in human and mouse brains. Subsequent analysis of TDP-43 binding miRNAs suggests that target genes are enriched in functions involving synaptic activities. We further identify a novel miRNA (miR-NID1) processed from the intron 5 of human neurexin 1, NRXN1, and show that miR-NID1 represses NRXN1 expression by binding to TDP-43. Our results are in accordance with previously published data indicating TDP-43 through binding of specific miRNAs to play roles in neurodevelopmental activities and neurological disorders and further our understanding of TDP-43 function.
authors.affiliation: Laboratory of Noncoding RNA, Institute of Biophysics, Chinese Academy of Sciences, Beijing 100101, China; University of Chinese Academy of Sciences, Beijing 100049, China.
authors.forename: Zhen
authors.initials: Z
authors.lastname: Fan
authors.affiliation: Laboratory of Noncoding RNA, Institute of Biophysics, Chinese Academy of Sciences, Beijing 100101, China; University of Chinese Academy of Sciences, Beijing 100049, China.
authors.forename: Xiaowei
authors.initials: X
authors.lastname: Chen
authors.affiliation: Laboratory of Noncoding RNA, Institute of Biophysics, Chinese Academy of Sciences, Beijing 100101, China. Electronic address: chenrs@sun5.ibp.ac.cn.
authors.forename: Runsheng
authors.initials: R
authors.lastname: Chen
mesh_terms: D000818:Animals; D001483:Base Sequence; D002135:Calcium-Binding Proteins; D015816:Cell Adhesion Molecules, Neuronal / Q000235:genetics*; D002460:Cell Line; D004268:DNA-Binding Proteins / Q000235:genetics*; D005786:Gene Expression Regulation; D006801:Humans; D051379:Mice; D035683:MicroRNAs / Q000235:genetics; D008969:Molecular Sequence Data; D009419:Nerve Tissue Proteins / Q000235:genetics*; D019006:Neural Cell Adhesion Molecules / Q000235:genetics*; D009690:Nucleic Acid Conformation; D011485:Protein Binding; D012333:RNA, Messenger / Q000235:genetics; D017423:Sequence Analysis, RNA; D059467:Transcriptome
chemical_list: D002135:Calcium-Binding Proteins; D015816:Cell Adhesion Molecules, Neuronal; D004268:DNA-Binding Proteins; D035683:MicroRNAs; C539628:NRXN1 protein, human; D009419:Nerve Tissue Proteins; D019006:Neural Cell Adhesion Molecules; C527193:Nrxn1 protein, mouse; D012333:RNA, Messenger
keywords: CA repeat; NRXN1; Novel intronic miRNA; TDP-43