Morriss Ginny R, Cooper Thomas A
Department of Pathology and Immunology, Baylor College of Medicine, Houston, TX, 77030, USA.
Department of Molecular and Cellular Biology, Baylor College of Medicine, Houston, TX, 77030, USA.
Hum Genet. 2017 Sep;136(9):1247-1263. doi: 10.1007/s00439-017-1807-6. Epub 2017 May 8.
An emerging class of long noncoding RNAs (lncRNAs) function as decoy molecules that bind and sequester proteins thereby inhibiting their normal functions. Titration of proteins by lncRNAs has wide-ranging effects affecting nearly all steps in gene expression. While decoy lncRNAs play a role in normal physiology, RNAs expressed from alleles containing nucleotide repeat expansions can be pathogenic due to protein sequestration resulting in disruption of normal functions. This review focuses on commonalities between decoy lncRNAs that regulate gene expression by competitive inhibition of protein function through sequestration and specific examples of nucleotide repeat expansion disorders mediated by toxic RNA that sequesters RNA-binding proteins and impedes their normal functions. Understanding how noncoding RNAs compete with various RNA and DNA molecules for binding of regulatory proteins will provide insight into how similar mechanisms contribute to disease pathogenesis.
一类新兴的长链非编码RNA（lncRNA）作为诱饵分子发挥作用，它们结合并隔离蛋白质，从而抑制其正常功能。lncRNA对蛋白质的滴定作用具有广泛影响，几乎影响基因表达的所有步骤。虽然诱饵lncRNA在正常生理过程中发挥作用，但含有核苷酸重复扩增的等位基因所表达的RNA可能具有致病性，因为蛋白质隔离会导致正常功能的破坏。本综述重点关注通过隔离竞争性抑制蛋白质功能来调节基因表达的诱饵lncRNA之间的共性，以及由隔离RNA结合蛋白并阻碍其正常功能的毒性RNA介导的核苷酸重复扩增疾病的具体例子。了解非编码RNA如何与各种RNA和DNA分子竞争结合调节蛋白，将有助于深入了解类似机制如何导致疾病发病。
