Sadova Anastasia A, Kupriyanova Natalia S, Pavlova Galina V
Academic Chair of Biochemistry and Molecular Biology, Faculty of General Medicine, Pirogov Russian National Research Medical University, 117997 Moscow, Russia.
Lab. of Genome Organization, Institute of Gene Biology, Russian Academy of Sciences, 119334 Moscow, Russia.
Cancers (Basel). 2020 Jul 28;12(8):2090. doi: 10.3390/cancers12082090.
Ribosomal DNA is one of the most conserved parts of the genome, especially in its rRNA coding regions, but some puzzling pieces of its noncoding repetitive sequences harbor secrets of cell growth and development machinery. Disruptions in the neat mechanisms of rDNA orchestrating the cell functioning result in malignant conversion. In cancer cells, the organization of rRNA coding genes and their transcription somehow differ from that of normal cells, but little is known about the particular mechanism for this switch. In this study, we demonstrate that the region ~2 kb upstream of the rDNA promoter is transcriptionally active in one type of the most malignant human brain tumors, and we compare its expression rate to that of healthy human tissues and cell cultures. Sense and antisense non-coding RNA transcripts were detected and mapped, but their secondary structure and functions remain to be elucidated. We propose that the transcripts may relate to a new class of so-called promoter-associated RNAs (pRNAs), or have some other regulatory functions. We also hope that the expression of these non-coding RNAs can be used as a marker in glioma diagnostics and prognosis.
核糖体DNA是基因组中最保守的部分之一,尤其是在其rRNA编码区域,但它的一些非编码重复序列中令人费解的片段隐藏着细胞生长和发育机制的秘密。核糖体DNA协调细胞功能的精确机制遭到破坏会导致恶性转化。在癌细胞中,rRNA编码基因的组织及其转录在某种程度上与正常细胞不同,但对于这种转变的具体机制知之甚少。在本研究中,我们证明了rDNA启动子上游约2 kb的区域在一种最恶性的人类脑肿瘤中具有转录活性,并且我们将其表达率与健康人类组织和细胞培养物的表达率进行了比较。检测并绘制了正义和反义非编码RNA转录本,但它们的二级结构和功能仍有待阐明。我们提出这些转录本可能与一类新的所谓启动子相关RNA(pRNA)有关,或者具有其他一些调节功能。我们还希望这些非编码RNA的表达可以用作胶质瘤诊断和预后的标志物。