The biosynthesis of ribosomes is a complex process that requires the coordinated action of many factors and a huge energy investment from the cell. Ribosomes are essential for protein production, and thus for cellular survival, growth and proliferation. Ribosome biogenesis is initiated in the nucleolus and includes: the synthesis and processing of ribosomal RNAs, assembly of ribosomal proteins, transport to the cytoplasm and association of ribosomal subunits. The disruption of ribosome biogenesis at various steps, with either increased or decreased expression of different ribosomal components, can promote cell cycle arrest, senescence or apoptosis. Additionally, interference with ribosomal biogenesis is often associated with cancer, aging and age-related degenerative diseases. Here, we review current knowledge on impaired ribosome biogenesis, discuss the main factors involved in stress responses under such circumstances and focus on examples with clinical relevance.

• Keywords
• aging, cancer, p53, ribosome biogenesis, ribosomopathy,
• MeSH
• Organelle Biogenesis MeSH
• Humans MeSH
• Neoplasms metabolism   MeSH
• Ribosomal Proteins metabolism   MeSH
• Ribosomes metabolism   MeSH
• Aging metabolism   MeSH
• Animals MeSH
• Check Tag
• Humans MeSH
• Animals MeSH
• Publication type
• Journal Article MeSH
• Research Support, Non-U.S. Gov't MeSH
• Review MeSH
• Names of Substances
• Ribosomal Proteins MeSH

Ribosome biosynthesis, best studied in opisthokonts, is a highly complex process involving numerous protein and RNA factors. Yet, very little is known about the early stages of pre-18S rRNA processing even in these model organisms, let alone the conservation of this mechanism in other eukaryotes. Here we extend our knowledge of this process by identifying and characterizing the essential protein TbUTP10, a homolog of yeast U3 small nucleolar RNA-associated protein 10 - UTP10 (HEATR1 in human), in the excavate parasitic protist Trypanosoma brucei. We show that TbUTP10 localizes to the nucleolus and that its ablation by RNAi knock-down in two different T. brucei life cycle stages results in similar phenotypes: a disruption of pre-18S rRNA processing, exemplified by the accumulation of rRNA precursors, a reduction of mature 18S rRNA, and also a decrease in the level of U3 snoRNA. Moreover, polysome profiles of the RNAi-induced knock-down cells show a complete disappearance of the 40S ribosomal subunit, and a prominent accumulation of the 60S large ribosomal subunit, reflecting impaired ribosome assembly. Thus, TbUTP10 is an important protein in the processing of 18S rRNA.

• Keywords
• Pre-18S rRNA processing, Ribosomal RNA, Trypanosoma, U3 snoRNA, UTP10,
• MeSH
• Genes, Essential * MeSH
• RNA, Small Nucleolar metabolism   MeSH
• RNA Processing, Post-Transcriptional * MeSH
• RNA-Binding Proteins genetics   metabolism   MeSH
• Protozoan Proteins genetics   metabolism   MeSH
• RNA, Ribosomal, 18S metabolism   MeSH
• Trypanosoma brucei brucei enzymology   metabolism   MeSH
• Gene Silencing MeSH
• Publication type
• Journal Article MeSH
• Research Support, Non-U.S. Gov't MeSH
• Names of Substances
• RNA, Small Nucleolar MeSH
• RNA-Binding Proteins MeSH
• Protozoan Proteins MeSH
• RNA, Ribosomal, 18S MeSH