A potential role of extended simple sequence repeats in competing endogenous RNA crosstalk

MicroRNA (miRNA)-mediated crosstalk between coding and non-coding RNAs of various types is known as the competing endogenous RNA (ceRNA) concept. Here, we propose that there is a specific variant of the ceRNA language that takes advantage of simple sequence repeat (SSR) wording. We applied bioinformatics tools to identify human transcripts that may be regarded as repeat-associated ceRNAs (raceRNAs). Multiple protein-coding transcripts, transcribed pseudogenes, long non-coding RNAs (lncRNAs) and circular RNAs (circRNAs) showing this potential were identified, and numerous miRNAs were predicted to bind to SSRs. We propose that simple repeats expanded in various hereditary neurological diseases may act as sponges for miRNAs containing complementary repeats that would affect raceRNA crosstalk. Based on the representation of specific SSRs in transcripts, expression data for SSR-binding miRNAs and expression profiling data from patients, we determined that raceRNA crosstalk is most likely to be perturbed in the case of myotonic dystrophy type 1 (DM1) and type 2 (DM2).

由微小RNA（microRNA，miRNA）介导的各类编码RNA与非编码RNA之间的串扰，被称为内源竞争RNA（competing endogenous RNA，ceRNA）假说。本研究提出，存在一类依托简单序列重复（simple sequence repeat，SSR）序列特征的特殊ceRNA调控模式。本研究运用生物信息学工具，筛选出可归类为重复相关竞争内源RNA（repeat-associated ceRNAs，raceRNAs）的人类转录本。共鉴定得到多个具备该调控潜能的蛋白编码转录本、转录假基因、长链非编码RNA（long non-coding RNAs，lncRNAs）以及环状RNA（circular RNAs，circRNAs），并预测到大量可结合SSR序列的微小RNA。本研究进一步提出，各类遗传性神经系统疾病中发生扩增的简单重复序列，可作为携带互补重复序列的微小RNA的海绵，进而干扰raceRNA的串扰调控。基于转录本中特定SSR的分布特征、结合SSR的微小RNA的表达数据，以及患者的表达谱数据，本研究证实，1型肌强直性营养不良（myotonic dystrophy type 1，DM1）与2型肌强直性营养不良（myotonic dystrophy type 2，DM2）患者体内的重复相关竞争内源RNA串扰极有可能受到扰动。