Reviews & Analysis

RNAi is used for genome-wide functional screens in cultured cells and animals. New experimental and bioinformatics approaches, including the combination of RNAi with genome-editing strategies, has improved the efficacy of RNAi screening and follow-up experiments, and enhanced our understanding of gene function and regulatory networks.

Structural maintenance of chromosomes (SMC) complexes — cohesin, condensin and the SMC5/6 complex — regulate sister chromatid cohesion, chromosome condensation, and DNA replication, repair and transcription. Insights into how they may execute such a range of functions are emerging from analyses of their chromosomal binding, combined with their capacity to act as intermolecular and intramolecular linkers of DNA molecules.

Lamellipodial protrusion is powered by actin polymerization that is mediated through the actin-related protein 2/3 (ARP2/3)-induced nucleation of branched actin networks and the elongation of actin filaments. These processes are regulated by positive and negative feedback loops centred around the GTPase RAC, and the balance between them determines lamellipodial and directional persistence during cell migration.

Bidirectional movement by oppositely directed motors attached to the same cargo is frequently described as a 'tug of war'. However, some studies suggest that inhibiting one motor diminishes motility in both directions. To resolve this paradox, three bidirectional transport models, termed microtubule tethering, mechanical activation and steric disinhibition, are proposed, and a general mathematical modelling framework for bidirectional cargo transport is described.

microRNAs (miRNAs) promote and stabilize cells fates during the differentiation of stem and progenitor cells into muscle, blood, skin and neural tissues. These miRNAs are part of complex networks that tightly regulate their function at multiple levels: transcription, biogenesis, stability and target site availability, as well as their cooperation with other miRNAs and RNA- binding proteins.

Mobile RNAs function in antiviral defence, cell signalling and gene expression regulation, and might also mediate transgenerational epigenetic inheritance. Genetic and molecular studies in plants and nematodes have begun to provide insights into the mechanisms underlying RNA movement, its functions and the nature of mobile RNA molecules.

Recent technical advances are expanding our understanding of how lysine acetylation, as well as other metabolite-sensitive acylations, regulates various cellular processes. Emerging findings point to new functions for different acylations and deacylating enzymes, and clarify the intricate link between lysine acetylation and cellular metabolism.

In animals, microRNAs (miRNAs) are ∼22 nucleotides in length and are produced by two RNase III proteins — Drosha and Dicer. Their biogenesis is regulated at multiple levels, including at the level of miRNA transcription; by Drosha and Dicer processing; by their modification through RNA editing, RNA methylation, uridylation and adenylation; Argonaute loading; and by RNA decay.

The optogenetic toolkit has rapidly expanded to include various proteins and cellular functions, such as cell signalling, that can be controlled by light. The practical considerations in using and deciding between optogenetic systems, such as systems that use light-oxygen-voltage (LOV) domains, phytochrome proteins, CRYPTOCHROME 2 (CRY2) and the fluorescent protein Dronpa, are now well defined.

Linear ubiquitylation was initially identified owing to its function in canonical nuclear factor-κB activation. Recent studies have revealed the involvement of linear ubiquitin chains in the regulation of other signalling pathways and cell death, and in several diseases including cancer, which highlights the unexpected importance of this form of ubiquitylation.

Members of the polo-like kinase (PLK) family are crucial regulators of cell cycle progression, centriole duplication, mitosis, cytokinesis and the DNA damage response. Recent structural and molecular studies have revealed how such processes depend on the tight regulation of PLK abundance, activity, localization and interactions with other proteins, and how dysregulation may be associated with disease.

Classically associated with ageing and cancer, cellular senescence also seems to function in tissue remodelling during embryonic development and tissue repair, in which senescent cells are cleared before regeneration. Senescence is therapeutically relevant, as it can be either beneficial or detrimental in different diseases.

Nucleotide excision repair (NER) eliminates structurally diverse DNA lesions by repairing helix-distorting damage throughout the genome as well as transcription-blocking lesions. NER defects result in a wide range of disease phenotypes and recent findings have led to a mechanistic model that explains the complex genotype–phenotype correlations of transcription-coupled repair disorders.

Large-scale methodologies to facilitate the systematic measurement of protein abundance, translation level, turnover rate, post-translational modification, localization and interaction with other proteins are beginning to enable dynamic assessments of proteomes at the single-cell level.

Although they are damaging when produced in large quantities, low levels of reactive oxygen species (ROS) can function within specific signalling pathways, based on the reversible oxidation of crucial Cys residues in reduction–oxidation (redox)-sensitive target proteins. Understanding these pathways has implications for metabolic regulation, innate immunity, stem cell biology, tumorigenesis and ageing.

Protein aggregation and amyloid deposition are associated with a wide range of medical disorders, including Alzheimer's disease and type II diabetes. Studies into the amyloid state are revealing fundamental principles that underlie the maintenance of protein homeostasis, and the origins of aberrant protein behaviour and disease.

Homologous recombination is crucial for genome stability and for genetic exchange. Our knowledge of homology search, the step in this process that explores the genome for homologous sequences to enable recombination, has been increased by recent methodological advances. These insights can be integrated into a mechanistic model of homology search.

Epithelial cells display dynamic behaviours, such as rearrangement, movement and shape changes. Evidence suggests that the remodelling of cell junctions, especially adherens junctions (AJs), has major roles in controlling these behaviours. It is also clear that RHO GTPases and their effectors regulate actin polymerization and actomyosin contraction at AJs during epithelial reshaping.

Epigenetic memory maintains gene expression states through cell generations, in the absence of the initiating signals or changes in DNA sequence. Our understanding of how the Polycomb (PcG) and Trithorax (TrxG) group proteins confer long-term, mitotically heritable memory by sustaining silent and active gene expression states, respectively, during DNA replication and mitosis, is increasing.

As in animals, plant stem cells reside in stem cell niches, which produce signals that regulate the balance between self-renewal and differentiation into new tissues. Continuous organ production that is characteristic of plant growth requires a robust regulatory network to maintain this balance. Elucidating this network provides an opportunity to compare plant and animal stem cell strategies.