Browse Articles

Emerging data support that RNA methylation plays important roles in RNA processing and metabolism. The methyltransferases Mettl3 and Mettl14 are shown to catalyse N⁶-methyladenosine (m⁶A) RNA modification in embryonic stem cells (ESCs). This m⁶A modification controls RNA metabolism and functions to destabilize mRNAs encoding developmental regulators to help sustain ESC self-renewal.

Epithelial cell layers need to be tightly regulated to maintain their integrity and correct function. Cell integration into epithelial sheets is now shown to depend on the N-WASP-regulated stabilization of cortical F-actin, which generates distinct patterns of apical–lateral contractility at E-cadherin-based cell–cell junctions.

Hair follicle stem cells (HFSCs) regenerate hair in response to Wnt signalling. Fuchs and colleagues use a genome-wide survey to discover that Wnt effectors TCF3, TCF4 and Groucho (TLE) coordinately repress Wnt target genes. They find that although β-catenin is dispensable for HSFC viability and proliferation, it is essential to relieve this repression to initiate hair follicle fate during the hair regeneration cycle.

Meyer and colleagues used live-cell imaging to study the spatial organization of Ca²⁺ signalling network components during cell migration.

Mutations in PINK1 cause early-onset Parkinson’s disease. Martins and colleagues find that the expression levels of genes involved in nucleotide metabolism are upregulated in a Drosophila pink1 mutant, and that this affects neuronal mitochondrial DNA synthesis. They find that enhancing nucleotide synthesis through genetics or pharmacological approaches rescues mitochondrial defects associated with PINK1 mutations.

Meiotic chromosome movement is needed for homologue pairing and synapsis. Watanabe and colleagues identify TERB1 as a protein needed for telomere mobility and attachment to the nuclear envelope, and for telomere enrichment of meiotic cohesin.

Yap and colleagues demonstrate that E-cadherin-based cell–cell junctions exhibit distinct patterns of apical and lateral contractility. They show that N-WASP-dependent stabilization of F-actin mediates increased apical junctional tension, and that modulation of intra-junctional tension differences can promote extrusion of cells from monolayers.

N⁶-methyladenosine (m6A) is an abundant internal modification of messenger RNA (mRNA) that has been reported recently in thousands of mammalian mRNAs and long non-coding RNAs (lncRNAs). Zhao and colleagues identify two methyltransferases responsible for this modification in mammalian cells, and demonstrate that they are required for embryonic stem cell self-renewal maintenance through an effect of the modification on the degradation of developmental regulator transcripts.

The San Francisco Declaration on Research Assessment (DORA), an initiative spearheaded by the American Society for Cell Biology, aims to reform research assessment.

In this issue, we present the first Review in a series covering current knowledge of genomic surveillance mechanisms.

Signal integration is central to the regulation of patterning during plant development. During lateral root initiation, a signalling pathway controlled by the phloem-secreted TDIF peptide is found to activate the auxin signalling pathway independently of auxin, through phosphorylation of ARF transcription factors by GSK3 (Shaggy-like) kinases.

Macroautophagy is a key regulator of cellular integrity and viability, but how the process facilitates apoptosis has remained poorly defined. It has now become clear that autophagy degrades the Fap-1 protein phosphatase, a critical negative regulator of apoptotic cell death signalled by the TNF receptor family member, Fas.

Generation of differentiated kidney cell types from pluripotent stem cells would be enormously useful for research and therapeutic purposes, but progress towards this goal has so far been limited. In three recent reports, mature kidney cell types and three-dimensional nephron-like structures were generated from pluripotent cells rapidly and efficiently. A detailed understanding of the signals that drive nephrogenesis proved critical for these achievements.

Stable RNA interference by shRNA provides a means to study multiple facets of gene function. Fellman and Lowe explore the rules of implementation of this silencing method in the vertebrate system for achieving maximal knockdown with minimal off-target effects.

Defects in DNA replication, or in the pathways evolved to correct DNA replication problems, can cause genomic instability and disease. Zeman and Cimprich discuss recent advances in our understanding of the cellular responses to replication stress.

Camargo and colleagues employed an RNAi screen to identify LKB1 as an upstream regulator of the Hippo pathway. They show that LKB1 regulates SCRIB localization through the MARK kinase, leading to regulation of the activity of YAP through MST1/2 kinases.

Auxin signalling controls events in plant development, but it is unclear how auxin sensitivity is regulated. Hwang and colleagues find that phosphorylation of AUXIN RESPONSE FACTORS (ARFs) by BRASSINOSTEROID-INSENSITIVE 2 (BIN2) suppresses their interaction with the repressors AUX/IAA to enhance the transcription of auxin target genes, which is essential for lateral root emergence.

Differentiation of pluripotent cells into renal lineages has had limited success so far. Melissa Little and colleagues have used defined medium conditions that induce posterior primitive streak and intermediate mesoderm using growth factors used during normal embryogenesis. This results in the synchronous induction of both components of the kidney, the ureteric bud and metanephric mesenchyme, which form a self-organizing nephron structure in vitro.

Rab GTPases are important mediators of vesicle trafficking, but how they are regulated is not clear. Thompson and colleagues find that calcium efflux through the ion channel P2XA in the Dictyostelium discoideum contractile vacuole leads to activation of the Rab GTPase-activating protein CnrF, which in turn inactivates Rab11a to allow vacuole fusion.

Lowry and colleagues report the potential role of stem cell quiescence as a tumour suppressive mechanism. They show that although hair follicle stem cell activation allows tumour formation in response to oncogenic stimuli, tumours are not initiated during the quiescent phase of the hair cycle. They further find that the presence of Pten is important in maintaining hair follicle stem cell quiescence in this setting.