Ribosome's mode of function: myths, facts and recent results (original) (raw)
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New Insights into Ribosome Structure and Function
Cold Spring Harbor perspectives in biology, 2018
In the past 4 years, because of the advent of new cameras, many ribosome structures have been solved by cryoelectron microscopy (cryo-EM) at high, often near-atomic resolution, bringing new mechanistic insights into the processes of translation initiation, peptide elongation, termination, and recycling. Thus, cryo-EM has joined X-ray crystallography as a powerful technique in structural studies of translation. The significance of this new development is that structures of ribosomes in complex with their functional binding partners can now be determined to high resolution in multiple states as they perform their work. The aim of this article is to provide an overview of these new studies and assess the contributions they have made toward an understanding of translation and translational control.
The Eukaryotic Ribosome: Current Status and Challenges
Despite having been identified first, their greater degree of complexity has resulted in our understanding of eukaryotic ribosomes lagging behind that of their bacterial and archaeal counterparts. A much more complicated biogenesis program results in ribosomes that are structurally, biochemically, and functionally more complex. However, recent advances in molecular genetics and structural biology are helping to reveal the intricacies of the eukaryotic ribosome and to address many longstanding questions regarding its many roles in the regulation of gene expression.
Translating the Game: Ribosomes as Active Players
Frontiers in Genetics, 2018
Ribosomes have been long considered as executors of the translational program. The fact that ribosomes can control the translation of specific mRNAs or entire cellular programs is often neglected. Ribosomopathies, inherited diseases with mutations in ribosomal factors, show tissue specific defects and cancer predisposition. Studies of ribosomopathies have paved the way to the concept that ribosomes may control translation of specific mRNAs. Studies in Drosophila and mice support the existence of heterogeneous ribosomes that differentially translate mRNAs to coordinate cellular programs. Recent studies have now shown that ribosomal activity is not only a critical regulator of growth but also of metabolism. For instance, glycolysis and mitochondrial function have been found to be affected by ribosomal availability. Also, ATP levels drop in models of ribosomopathies. We discuss findings highlighting the relevance of ribosome heterogeneity in physiological and pathological conditions, as well as the possibility that in rate-limiting situations, ribosomes may favor some translational programs. We discuss the effects of ribosome heterogeneity on cellular metabolism, tumorigenesis and aging. We speculate a scenario in which ribosomes are not only executors of a metabolic program but act as modulators.
The Ribosome: A biochemist's mechano set
Biochemistry and Cell Biology, 1985
A ribosome, the cellular site for protein synthesis, is a very complex organelle composed of a myriad of macromolecular substructures. As models for this complex structure, we have been examining the structures and interactions of eukaryotic 5S and 5.8S rRNAs using adaptations of rapid RNA gel sequencing techniques. Estimates for their higher order structures have been proposed or evaluated, sites of interaction with other ribosomal components have been delineated, and the topography of these RNAs within the intact ribosome or 60S subunit have been examined. The results indicate that a universal structure for the ribosomal RNAs may only be present within the ribosome, that these molecules are probably present, at least in part, within the ribosomal interface, and that the bases for interactions with other ribosomal components are strongly dependent on their higher order structure. The experimental approaches which underlie these studies are considered in this review and the signific...
Pathways to Specialized Ribosomes: The Brussels Lecture
Specialized ribosomes" is a topic of intense debate and research whose provenance can be traced to the earliest days of molecular biology. Here, the history of this idea is reviewed, and critical literature in which the specialized ribosomes have come to be presently defined is discussed. An argument supporting the evolution of a variety of ribosomes with specialized functions as a consequence of selective pressures acting on a near-infinite set of possible ribosomes is presented, leading to a discussion of how this may also serve as a biological buffering mechanism. The possible relationship between specialized ribosomes and human health is explored. A set of criteria and possible approaches are also presented to help guide the definitive identification of "specialized" ribosomes, and this is followed by a discussion of how synthetic biology approaches might be used to create new types of special ribosomes.
Israel Journal of Chemistry, 2010
Abstract: This essay is a reflection on the ways the X‐ray structures of the ribosome are helping in the interpretation of cryogenic electron microscopy (cryo‐EM) density maps showing the translating ribosome in motion. Through advances in classification methods, cryo‐EM and single‐particle reconstruction methods have recently evolved to the point where they can yield an array of structures from a single sample (“story in a sample”), providing snapshots of an entire subprocess of translation, such as translocation or decoding.
Increasing Complexity of Ribosomes and Their Biogenesis
International Journal of Molecular Sciences
According to the classic ribosome model, developed in the 1960s and 1970s, its only function is to translate the four-letter nucleic acid code into the 20 amino acid peptide-code, while polymerizing amino acids into peptides with the help of a large complement of tRNAs and translation factors that cycle on and off the ribosome [...]