Minisatellites, also called variable number of tandem repeats (VNTRs), are a class of repetitive elements that may affect gene expression at multiple levels and have been correlated to disease. Their identification and role as expression quantitative trait loci (eQTL) have been limited by their absence in comparative genomic hybridization and single nucleotide polymorphisms arrays. By taking advantage of cap analysis of gene expression (CAGE), we describe a new example of a minisatellite hosting a transcription start site (TSS) which expression is dependent on the repeat number. It is located in the third intron of the gene nitrogen permease regulator like protein 3 (NPRL3). NPRL3 is a component of the GAP activity toward rags 1 protein complex that inhibits mammalian target of rapamycin complex 1 (mTORC1) activity and it is found mutated in familial focal cortical dysplasia and familial focal epilepsy. CAGE tags represent an alternative TSS identifying TAGNPRL3 messenger RNAs (mRNAs). TAGNPRL3 is expressed in red blood cells both at mRNA and protein levels, it interacts with its protein partner NPRL2 and its overexpression inhibits cell proliferation. This study provides an example of a minisatellite that is both a TSS and an eQTL as well as identifies a new VNTR that may modify mTORC1 activity.

中文翻译：

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人类微卫星拥有一个替代的RLRL3转录起始位点，以重复数依赖性方式驱动其表达

微型卫星，也称为可变数目的串联重复序列（VNTR），是一类重复元素，可能会在多个水平上影响基因表达，并与疾病相关。由于它们在比较基因组杂交和单核苷酸多态性阵列中的缺失，限制了它们作为表达定量性状基因座（eQTL）的鉴定和作用。通过利用基因表达的上限分析（CAGE），我们描述了一个小卫星的新例子，该小卫星具有一个转录起始位点（TSS），其表达取决于重复数。它位于氮通透酶调节子基因第三内含子，如蛋白质3（NPRL3）。NPRL3是针对rags 1蛋白复合物的GAP活性的组成部分，可抑制哺乳动物雷帕霉素复合物1（mTORC1）的靶标，并且发现其在家族性局灶性皮质发育异常和家族性局灶性癫痫中发生了突变。CAGE标签代表另一种TSS，可识别TAGNPRL3信使RNA（mRNA）。TAGNPRL3在红细胞中既在mRNA水平又在蛋白水平表达，它与其蛋白伴侣NPRL2相互作用，并且其过表达抑制细胞增殖。这项研究提供了一个既有TSS又有eQTL的微型卫星的例子，并确定了可能修饰mTORC1活性的新VNTR。