Department of Genetics and Evolution, University of Geneva, Geneva, Switzerland.
Max-Planck-Institute of Immunobiology and Epigenetics, Freiburg, Germany.
PLoS Genet. 2021 Nov 15;17(11):e1009843. doi: 10.1371/journal.pgen.1009843. eCollection 2021 Nov.
Intergenic transcription is a common feature of eukaryotic genomes and performs important and diverse cellular functions. Here, we investigate the iab-8 ncRNA from the Drosophila Bithorax Complex and show that this RNA is able to repress the transcription of genes located at its 3' end by a sequence-independent, transcriptional interference mechanism. Although this RNA is expressed in the early epidermis and CNS, we find that its repressive activity is limited to the CNS, where, in wild-type embryos, it acts on the Hox gene, abd-A, located immediately downstream of it. The CNS specificity is achieved through a 3' extension of the transcript, mediated by the neuronal-specific, RNA-binding protein, ELAV. Loss of ELAV activity eliminates the 3' extension and results in the ectopic activation of abd-A. Thus, a tissue-specific change in the length of a ncRNA is used to generate a precise pattern of gene expression in a higher eukaryote.
基因间转录是真核基因组的一个常见特征，它执行着重要且多样化的细胞功能。在这里，我们研究了果蝇 Bithorax 复合体中的 iab-8 ncRNA，并表明这种 RNA 能够通过序列非依赖性的转录干扰机制来抑制位于其 3' 端的基因的转录。尽管这种 RNA 在早期表皮和中枢神经系统中表达，但我们发现其抑制活性仅限于中枢神经系统，在野生型胚胎中，它作用于位于其下游的 Hox 基因 abd-A。中枢神经系统的特异性是通过由神经元特异性 RNA 结合蛋白 ELAV 介导的转录本的 3' 延伸来实现的。ELAV 活性的丧失消除了 3' 延伸，导致 abd-A 的异位激活。因此，在高等真核生物中，ncRNA 长度的组织特异性变化被用来产生精确的基因表达模式。
