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 ...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 tran- scription, 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.展开更多
基金supported in part by the grants from the National Natural Science Foundation of China(Nos.81071028 and 81172513 to R.D.)the National Basic Research Program of China(973 Program)(Nos.2012CB944600 and 2011CB510000 to R.D.)+2 种基金Program for New Century Excellent Talents(No.7603230006 to R.D.)the National Institutes of Health(NS079625 to P.J.)March of Dimes(FY13-354 to P.J.)
文摘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 tran- scription, 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.
