Reviews & Analysis

Repressive histone Lys methyltransferases (KMTs) mediate gene silencing by methylating histone H3 Lys 9 (H3K9), H3K27 and H4K20. Progress has been made in our understanding of the biochemical and functional properties of KMTs, the mechanisms of their recruitment to chromatin and the interplay between them.

Autophagy serves to degrade proteins during starvation. Recent progress has illuminated how, during starvation and nutrient repletion, autophagy can mobilize diverse cellular energy and nutrient stores, such as lipids, carbohydrates and iron, to salvage key metabolites that sustain and facilitate core anabolic functions.

Actomyosin-mediated contractility generates mechanical stress in animal cells and underlies muscle contraction, cell migration, cell division and tissue morphogenesis. Insight into the mechanics of actomyosin arrays that lack sarcomeric organization has revealed novel modes of force transmission and shown that diverse mechanical behaviours can arise from common molecular components.

The function of p53 as a tumour suppressor has been attributed to its ability to promote cell death or permanently inhibit cell proliferation. However, p53 can also contribute to cell survival by regulating various metabolic pathways to allow cells to adapt to mild metabolic stresses.

Recent studies in different species have increased our understanding of the factors and molecular mechanisms that underlie the specification of germ cells, which are the specialized cells that generate gametes. Moreover, studies are elucidating how these cells ensure that only germline-appropriate transcripts are translated to protect germ cell identity.

Recent studies have shown that nuclear export of mRNAs, which is a crucial step in the regulation of gene expression, can be selective in mammalian cells. Selective transport involves transcription-export complexes TREX and TREX-2 and controls biological processes such as DNA repair, haematopoiesis, proliferation and maintenance of pluripotency.

Recent studies have revealed that the RNase III enzymes Drosha and Dicer (including newly discovered Dicer isoforms) have non-canonical nuclear RNAi functions in various organisms. These include the regulation of transcription initiation and termination, and the processing of various RNA species.

During the G1–S phase transition of the cell cycle, a variable subset of previously 'licensed' origins of replication is activated to initiate DNA synthesis. Insight is being gained into the mechanisms underlying which origins are activated and when; these mechanisms are associated with nuclear organization, cell differentiation and replication stress.

The mitochondrial respiratory chain comprises large multi-subunit protein complexes that generate ATP. The crystal structure of the entire bacterial complex I was recently solved, providing novel insights into its core architecture, as well as the electron transfer and proton translocation pathways and the coupling between them.

Apoptosis, autophagy and necroptosis are discussed in the context of molecular mechanisms of programmed cell death during development and tissue homeostasis. The signals that dying cells produce can in turn induce the apoptosis or proliferation of neighbouring cells.

Mitochondrial proteases can be classified into subgroups depending on their function and location. They are highly specific and modulate biochemical activities that are essential for mitochondrial function and integrity. Impaired or dysregulated function of mitoproteases is associated with ageing and longevity, as well as with pathological conditions and human hereditary diseases.

RAF family kinases, which were first described over 30 years ago, primarily act as signalling relays downstream of RAS. Key mechanistic and structural studies are shaping our view of how RAF proteins and RAF-related pseudokinases are regulated; they also highlight the mechanisms underlying pathological RAF signalling and the unforeseen limitations of RAF inhibitors.

Somatic stem cells are responsible for tissue maintenance and repair throughout life. Studies on blood, skin and intestinal epithelium have revealed that multiple types of stem cells with distinct roles perform such regenerative functions. Moreover, stem cells have greater developmental flexibility than had previously been appreciated under stress conditions such as acute injury.

Advances in mass spectrometry-based proteomics are enabling the multidimensional analysis of protein properties such as abundance, localization, post-translational modifications and interactions for thousands of proteins. Complemented by new tools for data analysis and integration, these advances are transforming our understanding of various biological processes.

Recent technical advances have shown that scaffold proteins can hold members of a signal transduction cascade in place, focus enzyme activity at a particular site of action and/or provide a structural platform for the recruitment of signal transduction and signal termination enzymes.

Genome-wide mapping of chromatin contacts reveals the structural and organizational changes that the metazoan genome undergoes during cell differentiation. These changes involve entire chromosomes, which are influenced by contacts with nuclear structures such as the lamina, and local interactions mediated by transcription factors and chromatin looping.

Recent studies of mRNA distribution and translation show that, in addition to serving as the site of protein translocation into the endoplasmic reticulum (ER), ER-bound ribosomes translate a large fraction of mRNAs that encode cytosolic proteins. This, along with the discovery of many mechanisms for recruiting translation to the ER, suggests an expansive role for the ER in post-transcriptional gene expression.

Replication perturbation causes replication fork reversal (remodelling). Recent studies have visualized replication forks in metazoan cells and identified fork remodelling factors, showing fork reversal to be a global and regulated process with potential effects on replication termination, genome stability and the DNA damage response.

Transcription of eukaryotic protein-coding genes requires the assembly of a conserved initiation complex at promoter DNA. Structural information on this complex, which comprises RNA polymerase II and the general transcription factors, is beginning to reveal the mechanisms underlying the initial steps of transcription, such as the recognition and opening of promoter DNA.

RNA polymerase II (Pol II) is globally regulated by Mediator, a large, conformationally flexible protein complex with a variable subunit composition. These biochemical characteristics are fundamental for the ability of Mediator to control processes involved in transcription, including the organization of chromatin architecture and the regulation of Pol II pre-initiation, initiation, re-initiation, pausing and elongation.