Reviews & Analysis

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.

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.

Advances over the past decade in the development of imaging probes, microscopy techniques and image analysis have enabled researchers to gain a deeper knowledge and understanding of the dynamic processes of embryonic differentiation, patterning and morphogenesis through quantitative whole-animal imaging studies with high spatiotemporal resolution.

The results of transcriptome-wideN⁶-methyladenosine (m⁶A) mapping techniques have resolved many of the long-standing concerns regarding the physiological relevance of m⁶A, which suggests that this modification regulates mRNA fate and function. The identification of adenosine methylases and demethylases provides insights into the cellular pathways that involve m⁶A and indicates a role of m⁶A in physiological processes.

The epithelial polarity programme (EPP) is organized in response to extracellular cues and executed through the establishment of an apical–basal axis, intercellular junctions, epithelial-specific cytoskeletal rearrangements and a polarized trafficking machinery. Recent studies have provided insights into the interactions of the EPP with the polarized trafficking machinery and how they regulate epithelial polarization and depolarization.

The detailed motor mechanisms of individual kinesin family members are described in the context of their interactions with dynamic microtubules, and their contributions to important mechanistic events during bipolar spindle assembly and chromosome segregation in animal cells.

Studies of mouse models and advances in metabolomic analysis, particularly of haematopoietic stem cells, have revealed how metabolic cues from anaerobic glycolysis, bioenergetic signalling, the AKT–mTOR pathway, and Gln and fatty acid metabolism, affect the balance between stem cell self-renewal and differentiation. Understanding how metabolic pathways regulate fate decisions may be beneficial therapeutically.

Endocycling cells successively replicate their genomes without segregating chromosomes during mitosis and thereby become polyploid. Lack of chromosome segregation typically results from downregulation of mitotic cyclin-dependent kinase activity. Endocycles probably evolved many times, and the various endocycle mechanisms found in nature highlight the versatility of the cell cycle control machinery.