Showing papers in "Cell Reports in 2014"

TL;DR: A dense network of proteins interacting with METTL3, a component of the methyltransferase complex, is identified, and it is shown that three of them (WTAP, METTL14, and KIAA1429) are required for methylation.

TL;DR: A stringent experimental and computational workflow, capable of mapping more than 50,000 distinct phosphorylated peptides in a single human cancer cell line, is developed, suggesting that P-Tyr should be considered a functionally separate PTM of eukaryotic proteomes.

TL;DR: This work exploits massive Drosophila total RNA-sequencing data, >5 billion paired-end reads from >100 libraries covering diverse developmental stages, tissues, and cultured cells, to rigorously annotate >2,500 fruit fly circular RNAs, which exhibit commonalities and distinctions from mammalian circles.

TL;DR: It is demonstrated that the full four-helical bundle domain (4HBD) in the N-terminal region of MLKL is required and sufficient to induce its oligomerization and trigger cell death, and found that a patch of positively charged amino acids on the surface of the 4HBD binds to phosphatidylinositol phosphates (PIPs) and allows recruitment ofMLKL to the plasma membrane.

TL;DR: It is shown that hyperexcitability detected by clinical neurophysiological studies of ALS patients is recapitulated in induced pluripotent stem cell-derived motor neurons from patients harboring superoxide dismutase 1 (SOD1), C9orf72, and fused-in-sarcoma mutations.

TL;DR: Hallmarks of translation in ribosome footprints are shown: copurification with the large ribosomal subunit, response to drugs targeting elongation, trinucleotide periodicity, and initiation at early AUGs.

TL;DR: The authors performed whole-genome sequencing of DNA from 20 osteosarcoma tumor samples and matched normal tissue in a discovery cohort, as well as 14 samples in a validation cohort.

TL;DR: RNA profiling of macrophages and their exosomes shows that miRNA sorting to exosome is modulated by cell-activation-dependent changes of miRNA target levels in the producer cells, and the use of Dicer-deficient cells and reporter lentiviral vectors for miRNA activity shows that exosomal miRNAs are transferred from macrophage to ECs to detectably repress targeted sequences.

TL;DR: It is shown that embryonic microglia, which display a transiently uneven distribution, regulate the wiring of forebrain circuits and reveals roles for immune cells during normal assembly of brain circuits.

TL;DR: In this article, inosine in cellular RNA inhibits antiviral inflammatory and interferon responses by altering RLR interactions and restoring the expression of editing-active cytoplasmic ADARs.

TL;DR: The genomic profile of tFL shares similarities with that of germinal center B cell-type de novo DLBCL but also displays unique combinations of altered genes with diagnostic and therapeutic implications.

TL;DR: It is suggested that posttranscriptional modifications, notably 3' end adenylation and uridylation, exert opposing effects that may contribute, at least in part, to direct ncRNA sorting into EVs.

TL;DR: Two different events, ETC overload and partial ETC inhibition, promote superoxide-dependent tumor cell migration, invasion, clonogenicity, and metastasis, and specific scavenging of mitochondrial superoxide with mitoTEMPO blocked tumor cell Migration and prevented spontaneous tumor metastasis in murine and human tumor models.

TL;DR: It is shown that the ROS triggers the dissociation of NE from a membrane-associated complex into the cytosol and activates its proteolytic activity in a myeloperoxidase (MPO)-dependent manner.

TL;DR: It is concluded that nucleotide synthesis and cancer cell proliferation are supported by serine--rather than glycine--consumption, and therefore exogenous glycine cannot replace serine to supportcancer cell proliferation.

TL;DR: A modeling framework that integrates dynamic flux balance analysis with diffusion on a lattice and applied to engineered communities predicted and experimentally confirmed the species ratio to which a two-species mutualistic consortium converges and the equilibrium composition of a newly engineered three-member community.

TL;DR: A critical chaperome subnetwork that functions in aging and disease is identified using function, localization, interactome, and expression data sets to identify repression and induction clusters in human brain aging.

TL;DR: The utility of this method for measuring epigenomic changes following chemical perturbations is demonstrated and it is shown how reference normalization of ChIP-seq experiments enables the discovery of disease-relevant changes in histone modification occupancy.

TL;DR: Mouse as well as human pancreatic CTCs exhibit a very high expression of stromal-derived extracellular matrix (ECM) proteins, including SPARC, whose knockdown in cancer cells suppresses cell migration and invasiveness, pointing to their contribution of microenvironmental signals for the spread of cancer to distant organs.

TL;DR: It is shown that microglia sense SFAs and orchestrate an inflammatory process in the MBH that alters neuronal function when SFA consumption is high, and in this context, microglial depletion enhances leptin signaling and reduces food intake.

TL;DR: In this paper, the authors identify genes upregulated by bevacizumab treatment, including Fatty Acid Binding Protein 3 (FABP3) and FABP7, both of which are involved in fatty acid uptake.

TL;DR: The Sestrins are identified as GATOR2-interacting proteins that regulate the amino-acid-sensing branch of the mTORC1 pathway, which requires GATOR1 and the Rag GTPases, and the SestRins regulate the localization of m TORC1 in response to amino acids.

TL;DR: A role for H3K36 trimethylation in homologous recombination (HR) repair in human cells is defined and it is proposed that error-free HR repair within H3k36me3-decorated transcriptionally active genomic regions promotes cell homeostasis.

TL;DR: It is revealed that indole, a metabolite produced from the dissimilation of tryptophan, is able to modulate the secretion of glucagon-like peptide-1 from immortalized and primary mouse colonic L cells.

TL;DR: Al Alteration of Rb fox targets in some autistic brains is correlated with downregulation of all three Rbfox proteins, supporting the potential clinical relevance of the splicing-regulatory network.

TL;DR: It is demonstrated that neutrophils, typically viewed as cellular targets of IL-1β, themselves activate the NLRC4 inflammasome during acute Salmonella infection and are a major cell compartment for IL- 1β production during acute peritoneal challenge in vivo, which maximizes host proinflammatory and antimicrobial responses during pathogen challenge.

TL;DR: It is shown that Argonaute-2 (Ago2) and RNAi factors Dicer, TRBP and TRNC6A/GW182 are in the human nucleus and associate together in multi-protein complexes, demonstrating that RNAi can function in thehuman nucleus and suggesting that regulation of RNAi via small RNA loading of Ago2 differs between the cytoplasm and the nucleus.

TL;DR: This study found extension in lifespan, delayed onset of age-related metabolic diseases, and improved general health in mice fed a standard diet after SRT1720 supplementation and further supports the beneficial effects of SRT 1720 on health across the lifespan in mice.

TL;DR: The crystal structures of human cGAS are reported in its apo form, representing its autoinhibited conformation as well as in its cGAMP- and sulfate-bound forms, revealing switch-like conformational changes of an activation loop that result in the rearrangement of the catalytic site.

TL;DR: The findings implicate APOBEC activity as a key driver of PIK3CA mutagenesis and HPV-induced transformation and suggest that reduced exposure to exogenous carcinogens in HPV+ HNSCC creates a selective pressure that favors emergence of tumors with APOBec-mediated driver mutations.