Moss Tom, Sibai Dany S, Lessard Frédéric
St-Patrick Research Group in Basic Oncology, Cancer Division of the Quebec University Hospital Research Centre, Laval University, Quebec, Canada.
Department of Molecular Biology, Medical Biochemistry and Pathology, Faculty of Medicine, Laval University, Quebec, Canada.
J Cell Physiol. 2025 Aug;240(8):e70080. doi: 10.1002/jcp.70080.
The Ribosomal DNA (rDNA) in mammals is organised into large clusters of tandem repeats each of which encodes a single 47S precursor for the 18S, 5.8S, and 28S ribosomal RNAs (rRNAs) that is flanked upstream and downstream by an Intergenic Spacer (IGS) originally referred to as the Non-Transcribed Spacer (NTS). However, in certain cells and under certain environmental conditions the IGS has been found to be transcribed at low level to generate a range of "Noncoding" RNAs (ncRNAs). These ncRNAs have been implicated in the regulation of rRNA synthesis, rDNA silencing and protein sequestration in response to environmental and oncogenic stresses and tumour suppression. Here we review data on the generation, regulation and potential functions of these ncRNAs. We suggest that the majority of the ncRNAs originate from a failure of RNA polymerase I transcription termination by the Reb1- and Myb-related transcriptional "road-block" factor TTF1 and link their expression with tumour suppression.
哺乳动物的核糖体DNA(rDNA)被组织成串联重复的大簇,每个簇编码一个单一的47S前体,用于18S、5.8S和28S核糖体RNA(rRNA),其上游和下游侧翼是一个基因间隔区(IGS),最初称为非转录间隔区(NTS)。然而,在某些细胞和特定环境条件下,已发现IGS会以低水平转录,产生一系列“非编码”RNA(ncRNA)。这些ncRNA与rRNA合成的调控、rDNA沉默以及响应环境和致癌应激及肿瘤抑制的蛋白质隔离有关。在这里,我们综述了关于这些ncRNA的产生、调控和潜在功能的数据。我们认为,大多数ncRNA源于RNA聚合酶I转录终止的失败,这是由与Reb1和Myb相关的转录“路障”因子TTF1导致的,并将它们的表达与肿瘤抑制联系起来。