EDITOR PICKS THE EMBO JOURNAL Research articles Human long non-coding RNAs promote pluripotency and neuronal differentiation by association with chromatin modifiers and transcrip- tion factors Ng SY, Rory Johnson R and Stanton LW An array-based approach identifies hESC-specific novel long non-coding RNAs (lncRNAs) that are essential for the maintenance of pluripotency and indispensable for neuronal differentia- tion. A number of these lncRNAs directly interact with the pluripotency regula- tors SOX2 and PRC2. The EMBO Journal | doi:10.1038/emboj.2011.459 Redox signalling directly regulates TDP-43 via cysteine oxidation and disulphide cross-linking Cohen TJ, Hwang AW, Unger T, Trojanowski JQ and Lee VMY TDP-43 is a major constituent of inclu- sions characteristic of a number of neurodegenerative diseases. Oxidative stress induces reversible intra- and inter-molecular disulphide bond forma- tion at the second RNA-recognition motif impairing the solubility and the RNA processing function of TDP-43. The EMBO Journal | doi:10.1038/emboj.2011.471 CSPα knockout causes neurodegener- ation by impairing SNAP-25 function Sharma M, Burré J, Bronk P, Zhang Y, Xu W and Südhof TC The synaptic vesicle protein CSPα is a co-chaperone for the presynaptic SNARE protein SNAP-25 and regulates SNARE- complex assembly. Complementation experiments with CSPα knockout mice and SNAP-25 demonstrate that the destabilization of SNAP-25 alone is suffi- cient to cause neurodegeneration. The EMBO Journal | doi:10.1038/emboj.2011.467 Identification and characterization of a resident vascular stem/progenitor cell population in preexisting blood vessels Naito H, Kidoya H, Sakimoto S, Wakabayashi T and Takakura N The existence of vessel-resident endo- thelial stem cells remains a matter of debate. The results presented in this study support the existence of a CD31+/ CD45− side population in mouse vascular endothelia that carry features of endo- thelial stem cells/progenitors. The EMBO Journal | doi:10.1038/emboj.2011.465 Extraordinary transgressive pheno- types of hybrid tomato are influenced by epigenetics and small silencing RNAs Shivaprasad PV, Dunn RM, Santos BACM, Bassett A and Baulcombe DC Transgressive segregation in plant hybrids leads to the formation of heri- table phenotypes that are more extreme than either parent; the molecular basis of this phenomenon in unknown. This study identifies a number of small RNA loci that are more highly expressed in the hybrid than the parents, and corresponding repressed target genes that may mediate the transgressive phenotypes. The EMBO Journal | doi:10.1038/emboj.2011.458v Reviews Perspective EMBO Molecular Medicine Review DNA methylation: TET proteins – guardians of CpG islands? OPEN Williams K, Christensen J & Helin K DNA methylation is an epigenetic modification with important roles in transcriptional regulation during development. The recent finding that the TET family of proteins can convert methylcytosine to hydroxymethylcyto- sine suggests a potential mechanism for active DNA demethylation. EMBO reports | doi:10.1038/embor.2011.233 Regulation of TOR by small GTPases Durán RV & Hall MN Durán and Hall discuss recent findings on the regulation of mTOR. They specifi- cally focus on the role of small GTPases in this process and how their activity is modulated by a variety of upstream signals that are integrated into a single pathway through mTOR regulation. EMBO reports | doi:10.1038/embor.2011.257 Protein phosphatases and their regulation in the control of mitosis Mochida S & Hunt T Our understanding of the role of kinases in cell cycle control is rather advanced, but we are only scratching the surface of the reciprocal control by protein phosphatases. Mochida and Hunt discuss how removing phosphate moieties controls mitosis and how to move this emerging field forward. EMBO reports | doi:10.1038/embor.2011.263 Scientific Reports Assurance of mitochondrial integrity and mammalian longevity by the p62–Keap1–Nrf2–Nqo1 cascade Kwon J, Shin J & colleagues p62 is a known component of the autophagy machinery in vertebrates. This Scientific Report shows how p62 is also involved in maintaining mitochon- drial integrity and, as a consequence, prevents ageing through reduction of excess reactive oxygen species. EMBO reports | doi:10.1038/embor.2011.246 Synergism between altered cortical polarity and the PI3K/TOR pathway in the suppression of tumour growth Rossi F & Gonzalez C An unexpected crosstalk is revealed between the growth-promoting PI3K/ TOR pathway and cell polarity in the suppression of tumour formation in neural stem cells. The combination of pins loss-of-function and dietary restriction, PI3K mutation or TOR inhibition induces tumorigenesis in Drosophila larval brains. EMBO reports | doi:10.1038/embor.2011.230 Xenopus paraxial protocadherin inhibits Wnt/β-catenin signalling via casein kinase 2β Kietzmann A, Wang Y, Weber D & Steinbeisser H Steinbeisser and colleagues show that the cell adhesion molecule paraxial protocadherin not only activates the non-canonical Wnt/PCP pathway but, at the same time, also inhibits the canonical Wnt/β-catenin pathway through interaction with casein kinase 2. EMBO reports | doi:10.1038/embor.2011.240 5-Hydroxymethylcytosine: a new kid on the epigenetic block? Matarese F, Carrillo-de Santa Pau E & Stunnenberg HG This Perspective discusses recent advances in the genomic mapping of 5-hydoxymethylcytosine (5hmC) bases, and our understanding of their biologi- cal relevance. A critical meta-analysis highlights current challenges in char- acterizing the function of this putative epigenetic mark. Molecular Systems Biology | doi:10.1038/msb.2011.95 Research Articles Queueing up for enzymatic processing: correlated signaling through coupled degradation Cookson NA, Mather WH, Danino T, Mondragón-Palomino O, Williams RJ, Tsimring LS and Hasty J Overloaded enzymatic processes are shown to create indirect coupling between upstream components in cellular networks. This has important implications for the design of synthetic biology devices and for our understand- ing of currently inexplicable links within endogenous biological systems. Molecular Systems Biology | doi:10.1038/msb.2011.94 Programmed fluctuations in sense/ antisense transcript ratios drive sexual differentiation in S. pombe Bitton DA, Grallert A, Scutt PJ, Yates T, Li Y, Bradford JR, Hey Y, Pepper SD, Hagan IM and Miller CJ Strand-specific RNA sequencing of S. pombe reveals a highly structured programme of ncRNA expression at over 600 loci. Functional investigations show that this extensive ncRNA landscape controls the complex programme of sexual differentiation in S. pombe. Molecular Systems Biology | doi:10.1038/msb.2011.90 Temporal competition between differ- entiation programs determines cell fate choice Kuchina A, Espinar L, Çagˇatay T, Balbin AO, Zhang F, Alvarado A, Garcia-Ojalvo J and Süel GM An important cell fate decision in Bacillus subtilis is shown to be the result of a ‘molecular race’ between competing differentiation programs. The programs controlling competence initiation and spore formation progress independently, and without cross-talk, before cell fate choice. Molecular Systems Biology | doi:10.1038/msb.2011.88 The quantitative proteomes of human-induced pluripotent stem cells and embryonic stem cells Munoz J, Low TY, Kok YJ, Chin A, Frese CK, Ding V, Choo A and Heck AJR An in-depth proteomic comparison of human-induced pluripotent stem cells, and their parent fibroblast cells, with embryonic stem cells shows that the reprogramming process comprehensive- ly remodels protein expression levels, creating cells that closely resemble natural stem cells. Molecular Systems Biology | doi:10.1038/msb.2011.84 Regeneration of the heart Steinhauser ML and Lee RT In light of mixed results from clinical trials aiming at cardiac regeneration, it is worth revisiting both the foundations of this process and highlight recent advances that may portend future direc- tions in the field. EMBO Molecular Medicine | doi: 10.1002/ emmm.201100175 Research Articles Insulin biosynthesis in neuronal progenitors derived from adult hippocampus and the olfactory bulb OPEN Kuwabara T, Kagalwala MN, Onuma Y, Ito Y, Warashina M, Terashima K, Sanosaka T, Nakashima K, Gage FH and Asashima M Neural progenitor cells from the hippocampus and the olfactory bulb of type I and type II diabetic rats can be transplanted back into diabetic rats and produce insulin, demonstrating their potential as therapeutic agents. Upon transplantation into the pancreas, the neuronal cells not only express transcription factors characteristic for pancreatic beta cells, but also insulin levels in plasma increase and glucose levels in blood stabilize. EMBO Molecular Medicine | doi: 10.1002/ emmm.201100177 AKAP2 anchors PKA with aquaporin-0 to support ocular lens transparency OPEN Gold MG, Reichow SL, O’Neill SE, Weisbrod CR, Langeberg LK, Bruce JE, Gonen T and Scott JD Cataract is the leading cause of blind- ness in the world. Lens tissue can dete- riorate as a consequence of defective water and nutrient circulation through channels and transporters. Here, the authors show that AKAP2 directly binds AQP0 (a key water channel of the lens circulatory system), bringing PKA close enough to AQP0 to phosphorylate it, thus favoring water influx through the channel and preserving fluid circulation within the lens. EMBO Molecular Medicine | doi: 10.1002/ emmm.201100184 Dantrolene rescues arrhythmogenic RYR2 defect in a patient-specific stem cell model of catecholaminergic polymorphic ventricular tachycardia OPEN Jung CB, Moretti AM, Mederos y Schnitzler M, Iop L, Storch U, Bellin M, Dorn T, Ruppenthal S, Pfeiffer S, Goedel A, Dirschinger RJ, Seyfarth M, Lam JT, Sinnecker D, Gudermann T, Lipp P and Laugwitz KL Catecholaminergic polymorphic ventricular tachycardia (CPVT) is an inherited cardiac disease that, under physical and emotional stress, leads to life-threatening arrhythmia. Here, the authors generated the first human stem cell-based model for CPVT1, bearing a novel S406L missense mutation in RYR2, and demonstrated its suitability to reca- pitulate molecular and physiological aspects of the disease phenotype. EMBO Molecular Medicine | doi: 10.1002/ emmm.201100194 ©2012 EMBO EMBOencounters | Winter 2011|2012 | communications@embo.org 9