Revista de bioquímica y biología molecular Acceso abierto

Abstracto

Management of rRNA Transcription Activity in a Human Genome

NS Kupriyanova and AP Ryskov

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.