Opinion

Although non-coding RNAs have roles in transcription and chromatin function, nascent pre-mRNA is usually considered to be passive during these processes. Recently identified interactions between nascent pre-mRNAs and regulatory proteins suggest that both types of RNA regulate transcription and chromatin function.

In animal cells, actin is dynamically distributed between multiple coexisting arrays. Carlier and Shekhar propose that a global treadmilling process — whereby the various actin networks grow and shrink depending on the local activity of actin regulators — establishes a steady-state concentration of actin monomers that supports this homeostatic actin turnover.

The chemical modifications and structural features of mRNAs are highly dynamic. Together, they regulate the composition and function of the transcriptome by shaping RNA–protein interactions at different stages of the gene expression process.

The establishment of various coexisting actin networks supports a plethora of cellular processes and functions. How actin incorporation into these different networks is regulated to balance their growth and maintain homeostasis has remained elusive. Here, the authors propose that the internetwork competition for a limited pool of actin monomers underlies the homeostatic control of actin cytoskeleton organization.

Many proteins that canonically function in the cytosol can also localize to the nucleus. The authors propose that a distinct group of such proteins (which they name STRaNDs) engage in a particular mode of signal transduction, whereby in response to extracellular cues, the cytosolic protein transits to the nucleus and regulates gene expression without direct DNA binding.

Quante and Bird propose that the epigenome is modulated by the recruitment of cell type-specific DNA-binding proteins to short, abundant sequence motifs. The regulation of gene expression may thus be simplified by tuning gene expression in multigene blocks.

Members of the major facilitator superfamily are highly conserved transmembrane proteins that transport various small molecules, including nutrients, drugs, signalling molecules and waste products, across the plasma membrane. A novel model of their functional cycle provides insights into how these important transporters operate on the molecular level.

Catenins are typically considered to function at cell–cell junctions. However, it has recently become evident that multiple catenins can enter the nucleus and regulate gene expression. Thus, catenins might form complex networks, coupling membrane-associated signalling with transcriptional events.

How endocytic pits are formed in clathrin- and caveolin-independent endocytosis remains poorly understood. However, recent insight suggests that different forms of clathrin-independent endocytosis might involve the actin-driven focusing of membrane constituents, the lectin–glycosphingolipid-dependent construction of endocytic nanoenvironments and the use of Bin–Amphiphysin–Rvs (BAR) domain proteins as scaffolding modules.

Faithful chromosome segregation during mitosis depends on the bi-oriented attachment of chromosomes to spindle microtubules through their kinetochores. The precise regulation of kinetochore–microtubule attachment that ensures error-free mitosis may be explained by homeostatic principles involving receptors, a core control network, effectors and feedback control.

Dishevelled, EGL-10 and pleckstrin (DEP) domains carry out diverse functions by using different binding interfaces with well-defined structural features. It is becoming apparent that DEP domains mainly function in the spatial and temporal control of diverse signal transduction events by interacting with various partners at the plasma membrane.

Proteome maintenance was thought to be controlled in a cell-autonomous manner. However, recent findings suggest that proteostasis can be systemically regulated. Protein-folding defects systemically activate proteostasis mechanisms through signalling pathways that coordinate stress responses among tissues, and this may also coordinate ageing rates between tissues.

Cell death research was revitalized by the understanding that necrosis can occur in a regulated and genetically controlled manner. Although necroptosis is the most recognized form of regulated necrosis, other examples of this process have emerged. Understanding how these pathways are interconnected should enable regulated necrosis to be therapeutically targeted.

Autophagy was thought to be a purely cytosolic event. However, recent data highlight a role for the nucleus in autophagy regulation, showing that a complex network of histone modifications, microRNAs and transcription factors also control this process.

Structural and mechanistic studies have revealed common features of the way in which RNA and proteins are prepared for degradation by the exosome and proteasome, respectively. By extrapolating from what has been learnt about the proteasome, we may gain increased understanding of how its RNA counterpart, the exosome, is assembled and controlled.

A growing list of membrane trafficking regulators, particularly those affecting clathrin-mediated endocytosis, have independent functions in mitosis. This repurposing may have arisen from the functional flexibility of the membrane trafficking machinery.

Early mammalian blastocyst patterning involves symmetry breaking leading to lineage segregation. The classic models of lineage segregation cannot account for recent experimental data, and a new framework that regards the early mammalian embryo as a self-organizing system is put forward to explain these observations.

The function and regulation of poly(ADP-ribosyl)ation is partially understood. By contrast, little is known about intracellular mono(ADP-ribosyl)ation (MARylation) by ADP-ribosyl transferases. Recent findings indicate that MARylation regulates signalling and transcription by modifying key components in these processes, and that specific macrodomain-containing proteins 'read' and 'erase' this modification.

The transmembrane protein Crumbs is known to maintain epithelial polarity and regulate Notch and Hippo signalling via its short intracellular domain. Recent evidence now suggests that its extracellular domain has a conserved and fundamental role in mediating homophilic Crumbs–Crumbs interactions at cell–cell junctions.

The distribution of partitioning defective (PAR) proteins into two domains on the membrane is a hallmark of cell polarity. Domain boundaries are set by mechanical, biochemical and biophysical signals, and the resulting PAR domains define areas of cytosol specialization. Physical studies are now contributing to the understanding of the mechanisms underlying polarity establishment by PAR proteins.