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.
1 January 2016 in Biochemistry & Molecular Biology Journal
Protein synthesis is a fundamental cell process, performing by ribosomes. Ribosome biogenesis involves transcriptional and many post-transcriptional steps [1,2]. The control of cell growth is tightly connected with rRNA synthesis. In the human genome, rDNA clusters that comprise the so-called nucleolar organizers (NORs) span acrocentric chromosomes 13, 14, 15, 21, and 22. Moreover, many rDNA-similar segments can be detected on (NOR)-chromosomes. It is appreciated now days that the nucleolus plays a fundamental role in the regulation of molecular networks. RDNA consists of the zone coding functionally active rRNA promoting by RNA polymerase I (Pol I), and ribosomal intergenic spacer (rIGS). Today it is clear that rIGS comprises highly intricate structure consisting of a variety of functionally specific segments which have the property of activating under specific conditions, and can be easily transported to different genomic regions. Although similarity is very high in structure and function of rDNA repeating units in all vertebrates, a number of specific features are inherent to humans and higher primates [3,4]. The current model for transcriptional regulation of rRNA proposes two overlapping mechanisms. For short-term regulation, the transcription rate at active rDNA is altered by reversible modification of Pol I transcription factors, whereas long-term regulation is mediated by epigenetic mechanisms when specific chromatin modifications alter the ratio of active to silent copies of rRNA genes. Transcription of rRNA genes and maturation of rRNA play a central role in the complex network that controls cell growth and proliferation. A body of evidence argues that changes in nucleolar organizer (rDNA) activity can be not a result of tumorigenesis, but a cause of it. In this review we try to assess varied factors affecting rRNA and non-coding RNA (ncRNA) transcription activity, and correlate these data with surprisingly high content in the genome (high mobility) of the short segments surrounding ncRNA regions in the rIGS.
1 January 2016 in International Journal of Biotechnology and Bioengineering
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