Translational control by 80S formation and 60S availability: the central role of eIF6, a rate limiting factor in cell cycle progression and tumorigenesis.
Ribosome biogenesis and translation can be simplified as the processes of generating ribosomes and their use for decoding mRNA into a protein. Ribosome biogenesis has been efficiently studied in unicellular organisms like the budding yeast, allowing us a deep and basic knowledge of this process in growing cells. Translation has been modeled in vitro and in unicellular organisms. These studies have given us an important insight into the mechanisms and evolutionarily conserved aspects of ribosome biology. However, we advocate the need of the direct study of these processes in multicellular organisms. Analysis of ribosome biogenesis and translation in vivo in Metazoa and mammalian models is emerging and unveils the unexpected consequences of perturbed ribosome biogenesis and translation. Here, we will describe how one factor, eIF6, plays a crucial role both in the generation of the large ribosomal subunit and its availability for translation. From there, we will make specific conclusions on the physiological relevance of eIF6 in 80S formation, cell cycle progression and disease, raising the point that the control of gene expression may occur at the unexpected level of the large ribosomal subunit. In the future, the modulation of eIF6 binding to the 60S may be pharmacologically exploited to reduce the growth of cancer cells or ameliorate the phenotype of SDS syndrome.
Laboratory of Molecular Histology and Cell Growth, San Raffaele Scientific Institute, Milan, Italy.
Daniela
D
Brina
Stefano
S
Grosso
Annarita
A
Miluzio
Stefano
S
Biffo
D000818:Animals; D001855:Bone Marrow Diseases / Q000378:metabolism*; D002453:Cell Cycle / Q000502:physiology*; D002471:Cell Transformation, Neoplastic / Q000378:metabolism*; D039642:Eukaryotic Initiation Factors / Q000378:metabolism*; D010188:Exocrine Pancreatic Insufficiency / Q000378:metabolism*; D005786:Gene Expression Regulation / Q000502:physiology*; D006801:Humans; D008068:Lipomatosis / Q000378:metabolism*; D008954:Models, Biological; D014176:Protein Biosynthesis / Q000502:physiology*; D054658:Ribosome Subunits, Large / Q000378:metabolism / Q000502:physiology*; D000081003:Shwachman-Diamond Syndrome; D015398:Signal Transduction / Q000502:physiology
C109284:EIF6 protein, human; D039642:Eukaryotic Initiation Factors