Review Articles in 2017

The assembly and maintenance of heterochromatin are carried out by distinct mechanisms that include factors that bind nascent transcripts to recruit chromatin-modifying enzymes. The resulting post-translational modifications on heterochromatic histones contribute to the regulation of development by restricting lineage-specific gene expression.

The evolutionarily conserved mediator of RNA polymerase II transcription (Mediator) complex is a general regulator of transcription. Recent structural and functional studies have provided important insights into the mechanisms of transcription activation by Mediator and have also revealed a new function of this complex in genome organization and suggested that it could be therapeutically targeted in disease.

Gene expression programmes that are induced by inflammatory or oncogenic signals are controlled by shared chromatin regulators. Such chromatin dependencies are known to regulate oncogenes and inflammation-promoting genes and can be leveraged to combine and increase the effectiveness of immune-cell-based therapies with epigenetic therapies.

Cells activate a transcriptional response known as the mitochondrial unfolded protein response (UPR^mt) when mitochondrial integrity and function are impaired to promote their recovery. Recent insights into the regulation, mechanisms and functions of the UPR^mthave uncovered important links to ageing and ageing-associated diseases.

Structures in 5′ untranslated regions of eukaryotic mRNAs contribute to gene regulation by controlling cap-dependent and cap-independent translation initiation through diverse mechanisms. New structure probing technologies coupled with techniques such as compensatory mutagenesis will likely identify new structured RNA elements and help elucidate their function.

Sphingolipids are a major class of lipids, comprising various species with diverse functions. In addition to being structural elements of membranes, many sphingolipids are bioactive and regulate a myriad of cellular processes. Recent advances have shed new light on the complexity of sphingolipid metabolism and their various roles in physiology and disease.

Long intergenic non-coding RNAs (lincRNAs) do not overlap protein-coding genes, although some lincRNA genes have minimal coding potential and can include small open reading frames that encode functional peptides. lincRNA functions include RNA stabilization and transcription regulation and the remodelling of chromatin and genome architecture. Recent insights suggest that lincRNAs broadly serve to fine-tune the expression of neighbouring genes with remarkable tissue specificity.

Physical cues regulate stem cell fate and function during embryonic development and in adult tissues. The biophysical and biochemical properties of the stem cell microenvironment can be precisely manipulated using synthetic niches, which provide key insights into how mechanical stimuli regulate stem cell function and can be used to maintain and guide stem cells for regenerative therapies.

Coordinated movements of cell collectives are important for morphogenesis, tissue regeneration and cancer cell dissemination. Recent studies, mainly using novelin vitroapproaches, have provided new insights into the mechanisms governing this multicellular coordination, highlighting the key role of the mechanosensitivity of adherens junctions and mechanical cell–cell coupling in collective cell behaviours.

Mechanical cues from the microenvironment can be efficiently transmitted to the nucleus to engage in the regulation of genome organization and gene expression. Recent technological and theoretical progress sheds new light on the relationships between cell mechanics, nuclear and chromosomal architecture and gene transcription.

The uneven use of the synonymous amino acid codons in the transcriptome coupled with the relative concentrations of different tRNA species gives rise to non-uniform codon decoding rates by ribosomes, known as codon optimality. Codon optimality influences translation efficiency and fidelity, protein folding and mRNA decay.

Linker histones bind to nucleosomes and have been traditionally perceived as structural units of chromatin. Recent advances indicate that these histones have an active role in the control of chromatin architecture and function, participating in the regulation of gene expression, DNA replication and DNA repair.

Research over the past few decades has elucidated the biochemical mechanisms underlying insulin receptor signalling. Recent insights into the complexity of its temporal and tissue-specific regulation, which involves various combinations of signalling modules in different cell types, are shedding light on the pleiotropic effects of insulin action and the pathogenesis of insulin resistance.

AMP-activated protein kinase (AMPK) senses cellular energy levels and phosphorylates a variety of cellular substrates to inhibit or stimulate anabolic and catabolic processes, adjusting metabolism to energy needs. Recent studies have uncovered a crucial role of AMPK in the regulation of mitochondrial dynamics and mitophagy, further expanding its role in the control of cellular metabolism.

Soon after their discovery in 2010, Piezo channels became a paradigm for studying mechanosensitive ion channels. These channels respond to physiologically relevant forces in diverse cellular contexts, and their dysfunction has been linked to various diseases. We are now starting to understand gating mechanisms of Piezo channels and their key roles in physiology.

The transcription factors YAP and TAZ have recently emerged as being conserved transducers of mechanical signals into cells and mediators of processes such as proliferation, migration and cell fate decision. The roles of YAP-mediated and TAZ-mediated mechanotransduction have now been documented in many physiological and pathological contexts, providing novel insights into cellular mechano-responses and their consequences.

Atomic-resolution structures have recently been obtained for the intact spliceosome at different stages of the splicing cycle. These structural data have proved that the spliceosome is a protein-directed metalloribozyme and have increased our understanding of pre-mRNA splicing mechanisms, explaining a large body of existing genetic and biochemical data.

Ubiquitylation is a post-translational modification that modulates protein stability and regulates various cellular signalling pathways and cellular processes, including cell differentiation, proliferation and migration. Recent insights highlight its crucial role in development and how its deregulation is associated with several diseases.

Fluorescence nanoscopy enables the optical imaging of cellular components with resolutions at the nanometre scale. With the growing availability of super-resolution microscopes, nanoscopy methods are being increasingly applied. Quantitative, multicolour, live-cell nanoscopy and the corresponding labelling strategies are under continuous development.

tRNAs exist as diverse species, including sequence isoforms and nuclease-generated fragments, which are further functionally diversified by base modifications and various protein interactions. Perhaps unsurprisingly, tRNAs are now being implicated in various cellular processes beyond protein synthesis per se, including in stress responses, proliferation, cell fate determination and tumorigenesis.