Reviews & Analysis

RNA helicases of the DEAD box family are highly conserved enzymes with many roles in gene expression. Structural and mechanistic studies are uncovering the basis of their actions and have revealed roles not only in RNA unwinding but also in the remodelling of RNA–protein complexes and in the clamping of RNA to allow nucleation of larger complexes.

Clathrin-mediated endocytosis is a modular process that involves core and accessory adaptor proteins that package cargoes into vesicles, ultimately leading to their uptake. It is essential for many physiological processes in higher eukaryotes, including signal termination and exocytosis, so its components are rarely associated with disease.

RHO-specific guanine nucleotide dissociation inhibitors (RHOGDIs) had long been considered to be passive inhibitors of RHO GTPases, 'locking' them in an inactive state. However, recent findings suggest that they have integral roles in regulating RHO GTPases, controlling aspects such as stability, expression, activity and membrane localization.

In eukaryotes, RNA polymerases I, II and III synthesize RNAs, which are essential for life. Remarkably, plants have evolved two additional multisubunit RNA polymerases, RNA polymerases IV and V, to orchestrate non-coding RNA-mediated gene silencing processes. Their subunit compositions reveal that they evolved as specialized forms of RNA polymerase II.

The regulation of mitotic exit requires the rapid reversal of mitotic phosphorylation on a broad range of substrates. This requires not only inactivation of mitotic kinases but also activation of protein phosphatases, which work in regulatory networks to ensure that an interphase cell is correctly established.

Podosomes and invadopodia are actin-based dynamic protrusions of the plasma membrane of metazoan cells that represent sites of attachment to — and degradation of — the extracellular matrix. Progress has been made in our understanding of the regulation and function of these structures, and their role in human disease.

The regulation of apoptosis is essential for cell homeostasis and the survival of multicellular organisms, and excessive or diminished apopotosis can contribute to various diseases. The post-translational modification of apoptotic proteins by ubiquitylation is a key regulatory mechanism of cell death signalling cascades. Targeting apoptotic regulatory proteins in the ubiquitin proteasome system might afford clinical benefits.

The APC/C (anaphase-promoting complex, also known as the cyclosome) is an E3 ubiquitin ligase that ensures temporal order of the cell cycle by degrading different cell cycle regulators at specific time points. Recent studies have provided insights into how the APC/C recognizes its substrates and how it is itself regulated.

Muscle differentiation during development is regulated by transcription factor networks and microRNAs, and postnatal changes in muscle phenotype and mass are controlled by anabolic and catabolic signalling. Recent studies have elucidated the hierarchies of these signalling networks and have identified proteins that act both during development and in postnatal adaptation.

The ADP-ribosylation factor (ARF) and ARF-like (ARL) family of G proteins, which are known to regulate membrane traffic and organelle structure, are emerging as regulators of diverse processes, including lipid and cytoskeletal transport. Although traditionally viewed as part of a linear signalling pathway, ARFs and their regulators must now be considered to exist within functional networks, in which both the 'inactive' ARF and the regulators themselves can mediate distinct effects.

Cells exist within a three-dimensional microenvironment in which they are exposed to mechanical and physical cues. Disrupting these cues compromises tensional homeostasis, which suggests that there is complex interplay between the extracellular microenvironment and cellular function. As alterations in the extracellular matrix can sustain perturbed tensional homeostasis, it serves as a mechanically based memory-storage device.

Centromeric chromatin differs from bulk chromatin in many aspects, including a distinct organization and the presence of different histone variants. Studies have focused on elucidating the molecular and physical architecture of centromeric chromatin, as well as the properties that make it invaluable during chromosome segregation in mitosis.

Transcription termination is one of the least-understood processes in gene expression. However, recent studies have revealed common themes and principles between models of RNA polymerase II (Pol II) termination, including the poly(A)-dependent and Sen1-dependent pathways, and provided insight into the role of Pol II carboxy-terminal domain phosphorylation in this process.

In the ubiquitin network, a multitude of ubiquitin species is constantly decoded by ubiquitin-binding domains. To properly coordinate biological events, ubiquitylation depends on strict spatiotemporal regulation, which is achieved by compartmentalization, sequential series of ubiquitylation events and crosstalk with other post-translational modifications.

The initiation of translation in eukaryotes can be impeded by secondary structures in the mRNA upstream of the initiation codon. There is increasing evidence that several helicases act in concert to overcome such structures and to promote processive movement of the 40S ribosome subunit.

Cilium assembly requires the coordination of motor-driven intraflagellar transport, membrane trafficking and import of cilium-specific proteins through a barrier at the ciliary transition zone. Recent findings provide insights into how cilia might assemble and disassemble in synchrony with the cell cycle and achieve a steady-state length.

The genome encodes thousands of small RNAs that interact with PIWI proteins; these PIWI-interacting RNAs (piRNAs) mediate silencing of transposable elements and thereby protect the genome. New insights are being gained into the formation and functions of piRNAs, and where they exert their action in the cell.

Shoot branching is regulated by three classes of plant hormones, auxins, strigolactones (or derivatives) and cytokinins. In the past decade, two models — the auxin transport canalization-based model and the second messenger model — have been formulated to explain the mechanisms of bud activation and shoot branching control.

Asymmetric cell division is essential in many organisms, as it generates different cell types and maintains stem cell pools. The identification of key molecular players, and a comparison with the pathways in animals, allows a better mechanistic understanding of asymmetric cell division in plants and algae.

The signalling activity of cell adhesion molecules (CAMs) such as cadherins, immunoglobulin-like CAMs or integrins has been considered a direct consequence of their adhesive properties. However, in some cases CAMs can activate signalling in the absence of cell adhesion, which significantly extends their range of biological activities.