Abstract
Ribosomal RNA (rRNA) biogenesis takes place in the nucleolus, the most prominent condensate of the eukaryotic nucleus. The proper assembly and integrity of the nucleolus reflects the accurate synthesis and processing of rRNAs which in turn, as major components of ribosomes, ensure the uninterrupted flow of the genetic information during translation. Therefore, the abundant production of rRNAs in a precisely functional nucleolus is of outmost importance for the cell viability and requires the concerted action of essential enzymes, associated factors and epigenetic marks. The coordination and regulation of such an elaborate process depends on not only protein factors, but also on numerous regulatory non-coding RNAs (ncRNAs). Herein, we focus on RNA-mediated mechanisms that control the synthesis, processing and modification of rRNAs in mammals. We highlight the significance of regulatory ncRNAs in rRNA biogenesis and the maintenance of the nucleolar morphology, as well as their role in human diseases and as novel druggable molecular targets.
Highlights
The eukaryotic ribosome as a multimolecular machine composed of more than 80 proteins and four distinct types of ribosomal RNAs requires a dedicated and reliable procedure to become efficient and functional
Being a highly dynamic condensate, the nucleolus is composed of three distinct structural entities; the fibrillar center (FC) which is surrounded by the dense fibrillar center (DFC) and both are embedded in the granular component (GC) [4]
These well-defined subnucleolar compartments correspond to places where successively different stages of Ribosomal RNA (rRNA) biogenesis occur, starting from the rDNA transcription that occurs in the FC/DFC interface up to the early pre-60S and pre-40S assembly in the GC (Figure 1)
Summary
The eukaryotic ribosome as a multimolecular machine composed of more than 80 proteins and four distinct types of ribosomal RNAs (rRNAs) requires a dedicated and reliable procedure to become efficient and functional. Being a highly dynamic condensate, the nucleolus is composed of three distinct structural entities; the fibrillar center (FC) which is surrounded by the dense fibrillar center (DFC) and both are embedded in the granular component (GC) [4] These well-defined subnucleolar compartments correspond to places where successively different stages of rRNA biogenesis occur, starting from the rDNA transcription that occurs in the FC/DFC interface up to the early pre-60S and pre-40S assembly in the GC (Figure 1). RNA-mediated mechanisms have been described in all kingdoms of life with multiple regulatory roles in chromatin remodeling, cell cycle arrest, gene expression regulation at both the transcriptional and translational level and post-transcriptional modifications, usually providing a better understanding of human diseases, including cancer [20,21,22]. We focus on steps that take place inside the nucleolus, including rDNA transcription, rRNA processing and modification, and on the nucleolar disaggregation, in correlation to the development of human disorders
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