Trends in Biochemical Sciences最新文献

Methanogenic archaea (or methanogens) produce methane as a by-product of energy metabolism. Strategies for energy conservation differ across methanogens. Some lineages use an electron transport chain (ETC) with an endogenously produced heterodisulfide as an electron acceptor. Of late, culture-independent -omics techniques and genome editing tools have provided new insights into the evolution and function of bioenergetic complexes in methanogen ETCs, which will be the primary focus of this review. We will also discuss how the ETC enhances metabolic flexibility in methanogens and can even permit anaerobic respiration decoupled from methanogenesis. Finally, we expand on how innovations in the ETC might have enabled anaerobic methane oxidation in a closely related group of microorganisms called anaerobic methanotrophic archaea (ANME).

The cell is a dynamic system where millions of molecules of thousands different kinds act within a complex network with numerous feedback loops. Because we cannot pursue many targets simultaneously, 'big data' rarely yield useful leads. Comprehensive models can place the snippets obtained in simplified experimental conditions into a coherent picture.

The protein kinase Mps1 (also known as TTK) is a central component of the mitotic spindle assembly checkpoint (SAC), an essential self-monitoring system of the eukaryotic cell cycle that ensures accurate chromosome segregation by delaying the onset of anaphase until all chromosomes are properly bioriented on the mitotic spindle. Mps1 kinase is an important upstream regulator of the SAC and its recruitment to kinetochores critical for initiating SAC signaling. This review discusses the current understanding of Mps1 essential functions in the SAC, the emerging details of Mps1 role in error correction to safeguard genome stability, and the therapeutic potential of Mps1 inhibition for the treatment of cancer types associated with aberrant SAC signaling and chromosome segregation defects.

The RNA world hypothesis proposes that the early stages of the emergence of life on Earth comprised primitive cells in which RNA acted both to store genetic information and catalyze chemical reactions as RNA enzymes (ribozymes). Most contemporary ribozymes catalyze phosphoryl transfer reactions, but early ribozymes would have been required to catalyze a broader range of metabolic interconversions. None has been found in modern cells, yet ribozymes have been generated by in vitro evolution to catalyze several different chemical reactions, providing proof of principle of RNA-catalyzed metabolism. Recently, several different ribozymes that accelerate methyl or alkyl transfer have been isolated. As we discuss here, one of these, MTR1, uses a remarkably sophisticated catalytic mechanism involving nucleobase-mediated general acid catalysis.

Transcription factors (TFs) control gene expression by binding to specific DNA motifs in cis-regulatory elements. Cooperativity has been thought to ensure TF binding specificity. Recent research suggests that, at least in yeast, the role of cooperativity has probably been overemphasized. Consequently, synergy - the collective recruitment of the transcriptional machinery by TFs bound at multiple DNA sites - emerges as a more significant mechanism for achieving the specificity of the transcriptional response. Furthermore, I argue that the concentration of TFs within phase-separated nuclear condensates and their covalent modifications play an underappreciated but crucial role in sharpening transcriptional responses through complementary mechanisms. A model integrating cooperativity, synergy, post-translational modifications, and phase separation provides a comprehensive framework to explain dynamic, context-specific transcriptional responses in eukaryotes.