title: Towards understanding RNA-mediated neurological disorders.
abstract: RNA-mediated mechanisms of disease pathogenesis in neurological disorders have been recognized in the context of certain repeat expansion disorders. This RNA-initiated neurodegeneration may play a more pervasive role in disease pathology beyond the classic dynamic mutation disorders. Here, we review the mechanisms of RNA toxicity and aberrant RNA processing that have been implicated in ageing-related neurological disorders. We focus on diseases with aberrant sequestration of RNA-binding proteins, bi-directional transcription, aberrant translation of repeat expansion RNA transcripts (repeat-associated non-ATG (RAN) translation), and the formation of pathological RNA:DNA secondary structure (R-loop). It is likely that repeat expansion disorders arise from common mechanisms caused by the repeat expansion mutations. However, the context of the repeat expansion determines the specific molecular consequences, leading to clinically distinct disorders.
authors.affiliation: State Key Laboratory of Medical Genetics, Central South University, Changsha 410078, China. Electronic address: duanranhui@sklmg.edu.cn.
authors.forename: Ranhui
authors.initials: R
authors.lastname: Duan
authors.affiliation: Department of Human Genetics, Emory University School of Medicine, Atlanta 30322, USA.
authors.forename: Sumeet
authors.initials: S
authors.lastname: Sharma
authors.affiliation: State Key Laboratory of Medical Genetics, Central South University, Changsha 410078, China.
authors.forename: Qiuping
authors.initials: Q
authors.lastname: Xia
authors.affiliation: Department of Human Genetics, Emory University School of Medicine, Atlanta 30322, USA.
authors.forename: Kathryn
authors.initials: K
authors.lastname: Garber
authors.affiliation: Department of Human Genetics, Emory University School of Medicine, Atlanta 30322, USA. Electronic address: peng.jin@emory.edu.
authors.forename: Peng
authors.initials: P
authors.lastname: Jin
mesh_terms: D000818:Animals; D001483:Base Sequence; D006801:Humans; D009422:Nervous System Diseases / Q000235:genetics* / Q000378:metabolism / Q000628:therapy; D014176:Protein Biosynthesis; D012313:RNA / Q000235:genetics* / Q000378:metabolism; D016601:RNA-Binding Proteins / Q000378:metabolism; D014158:Transcription, Genetic
chemical_list: D016601:RNA-Binding Proteins; D012313:RNA
keywords: Neurodegeneration; R-loop; RAN translation; RNA toxicity; Repeat expansion