After the ribosome structure: how does translocation work?

Structures of the ribosomal large and small subunits have been solved to atomic resolution by X-ray crystallography. These structures provide a new foundation to address the complex process of protein biosynthesis by the ribosome. Translocation of the tRNA-mRNA complex is one of the most fascinating tasks performed by the ribosome. The impact of the crystal structures in understanding the molecular mechanism of translocation is highlighted in this review.     

After the ribosome structures: how are the subunits assembled?

The recent structures of the ribosome and the ribosomal subunits only heighten the intrigue of trying to understand how the ribosome is assembled. Biochemical and mechanistic studies have mapped out the basic series of protein binding events that occur, but we do not yet have a clear picture of the RNA conformational changes that must accompany the protein binding. Recent studies point to roles of protein folding chaperones and RNA helicases as facilitators of ribosome assembly, but the basic process of assembly seems to be encoded in the RNA sequences and can occur for the most part spontaneously in vitro, and quite possibly in vivo as well.     

Symmetry breakage in the vertebrate embryo: When does it happen and how does it work?

Asymmetric development of the vertebrate embryo has fascinated embryologists for over a century. Much has been learned since the asymmetric Nodal signaling cascade in the left lateral plate mesoderm was detected, and began to be unraveled over the past decade or two. When and how symmetry is initially broken, however, has remained a matter of debate. Two essentially mutually exclusive models prevail. Cilia-driven leftward flow of extracellular fluids occurs in mammalian, fish and amphibian embryos. A great deal of experimental evidence indicates that this flow is indeed required for symmetry breaking. An alternative model has argued, however, that flow simply acts as an amplification step for early asymmetric cues generated by ion flux during the first cleavage divisions. In this review we critically evaluate the experimental basis of both models. Although a number of open questions persist, the available evidence is best compatible with flow-based symmetry breakage as the archetypical mode of symmetry breakage.     

How does tmRNA move through the ribosome?

To test the structure of tmRNA in solution, cross-linking experiments were performed which showed two sets of cross-links in two different domains of tmRNA. Site-directed mutagenesis was used to search for tmRNA nucleotide bases that might form a functional analogue of a codon-anticodon duplex to be recognized by the ribosomal A-site. We demonstrate that nucleotide residues U85 and A86 from tmRNA are significant for tmRNA function and propose that they are involved in formation of a tmRNA element playing a central role in A-site recognition. These data are discussed in the frame of a hypothetical model that suggests a general scheme for the interaction of tmRNA with the ribosome and explains how it moves through the ribosome.     

The evolution of large size: how does Cope's Rule work?

Cope's Rule is the tendency for organisms in evolving lineages to increase in size over time. The concept is detailed in many textbooks, but has rarely been demonstrated. Many suggestions of the benefits of large body size exist, but none has yet been confirmed empirically. Using a large-scale analysis of recent studies, Kingsolver and Pfennig have now shown how size benefits survival, mating success and fecundity, and they provide convincing arguments for a mechanism that is capable of driving Cope's Rule.     

Treatment of COVID-19 with MSCs: how does it work?

Science China Life Sciences -     

Single-molecule biology: what is it and how does it work?

Biochemistry and structural biology are undergoing a dramatic revolution. Until now, we have tried to study subtle and complex biological processes by crude in vitro techniques, looking at average behaviors of vast numbers of molecules under conditions usually remote from those existing in the cell. Researchers have realized the limitations of this approach, but none other has been available. Now, we can not only observe the nuances of the behaviors of individual molecules but prod and probe them as well. Perhaps most important is the emerging ability to carry out such observations and manipulations within the living cell. The long-awaited leap to an in vivo biochemistry is at last underway.     

Healing the diabetic heart: does myocardial preconditioning work?

Diabetes mellitus-associated ischemic heart disease is a major public burden in industrialized countries. Reperfusion to a previously ischemic myocardium is obligatory to reinstate its function prior to irreversible damage. However, reperfusion is considered ‘a double-edged sword’ as reperfusion per se could augment myocardial ischemic damage, known as myocardial ischemia-reperfusion (I/R) injury. The brief and repeated cycles of I/R given before a sustained ischemia and reperfusion are represented as ischemic preconditioning, which protects the heart from lethal I/R injury. Few studies have demonstrated preconditioning-mediated cardioprotection in the diabetic heart. In contrast, considerable number of studies suggests that myocardial defensive effects of preconditioning are abolished in the presence of chronic diabetes mellitus that raised questions over preconditioning effects in the diabetic heart. It is evidenced that chronic diabetes mellitus-associated deficit in survival pathways, impaired function of mito-K_ATP channels, MPTP opening and high oxidative stress play key roles in paradoxically suppressed cardioprotective effects of preconditioning in the diabetic heart. These controversial results open up a new area of research to identify potential mechanisms influencing disparities on preconditioning effects in diabetic hearts. In this review, we discussed first the discrepancies on the modulatory role of diabetes mellitus in I/R-induced myocardial injury. Following this, we addressed whether preconditioning could protect the diabetic heart against I/R-induced myocardial injury. Moreover, potential mechanisms pertaining to the attenuated cardioprotective effects of preconditioning in the diabetic heart have been delineated. These are important to be understood for better exploitation of preconditioning strategies in limiting I/R-induced myocardial injury in the diabetic heart.     

Integration of omics data: how well does it work for bacteria?

In the current omics era, innovative high-throughput technologies allow measuring temporal and conditional changes at various cellular levels. Although individual analysis of each of these omics data undoubtedly results into interesting findings, it is only by integrating them that gaining a global insight into cellular behaviour can be aimed at. A systems approach thus is predicated on data integration. However, because of the complexity of biological systems and the specificities of the data-generating technologies (noisiness, heterogeneity, etc.), integrating omics data in an attempt to reconstruct signalling networks is not trivial. Developing its methodologies constitutes a major research challenge. Besides for their intrinsic value towards health care, environment and industry, prokaryotes are ideal model systems to further develop these methods because of their lower regulatory complexity compared with eukaryotes, and the ease with which they can be manipulated. Several successful examples outlined in this review already show the potential of the systems approach for both fundamental and industrial applications, which would be time-consuming or impossible to develop solely through traditional reductionist approaches.     

The non‐existent aging program: how does it work?

Summary Aging and lifespan determination have been viewed, in the most well-accepted theories, as nonprogrammatic, and are thought to result from the evolutionary selection for early fitness at the expense of late survival. Here, recent data implicating potentially programmatic aspects of aging and lifespan determination are discussed, and analogies between programmed cell death and programmed organismal death are offered. It is hoped that the recognition of at least the possibility of a programmatic aspect, or aspects, to the determination of longevity and the process of aging will help to optimize our chances to identify appropriate therapeutic targets both for longevity enhancement and disease prevention.     

Promiscuous ligands and attractive cavities: how do the inhaled anesthetics work?

The inhaled anesthetics were officially introduced to American medicine more than 160 years ago and rank among the most important medical advances in our time. These drugs are used to render patients insensible over twenty million times each year and are the most dangerous of all drugs that physicians currently use. An entire medical specialty, anesthesiology, has arisen out of the need for the special training to administer them safely. Nevertheless, side effects, toxicity, and long-term cognitive problems continue to plague their use, especially in the very sick or aged. Hence, it is essential that we develop an understanding of their molecular pharmacology so that safer alternatives can be developed.     

Neurodegeneration: how does parkin prevent Parkinson's disease?

Mutations in parkin cause Parkinson's disease due to the loss of the ubiquitin-protein ligase activity of Parkin protein. Recent data suggest we may be beginning to understand the nature of the proteins that are targeted by Parkin and how these cause neuronal damage.     

How does gene expression clustering work?

Clustering is often one of the first steps in gene expression analysis. How do clustering algorithms work, which ones should we use and what can we expect from them?     

How does a legume nodule work?

Nitrogen fixation in legume root nodules requires biochemical cooperation between the plant and Rhizobium cells. Bacteroids contribute the N₂-fixing system and haem for leghaemoglobin, but apart from the production of the globin moiety of leghaemoglobin and the assimilation and export of the NH₃ produced, little is known about the contributions of the plant. It now appears that the plant cell may regulate the type and/or quantity of carbon compounds supplied to the Rhizobium bacteroids.