Showing papers in "Molecular Cell in 2013"

TL;DR: A quantitative model of aging is built using measurements at more than 450,000 CpG markers from the whole blood of 656 human individuals, aged 19 to 101, to measure the rate at which an individual's methylome ages, which is impacted by gender and genetic variants.

TL;DR: The discovery of ALKBH5 as another mammalian demethylase that oxidatively reverses m(6)A in mRNA in vitro and in vivo strongly suggests that the reversible m( 6)A modification has fundamental and broad functions in mammalian cells.

TL;DR: A cis-regulatory role of noncoding intronic transcripts on their parent coding genes is suggested, which largely accumulates to its sites of transcription, associates with elongation Pol II machinery, and acts as a positive regulator of Pol II transcription.

TL;DR: An overview of enhancer-associated modifications of histones and DNA is given and enzymatic activities involved in their dynamic deposition and removal are discussed and potential downstream effectors of these marks are described.

TL;DR: It is demonstrated that H19 modulates let-7 availability by acting as a molecular sponge, and this lncRNA is identified as an important regulator of the majorLet-7 family of microRNAs.

TL;DR: It is shown that phosphorylation of the autophagy-adaptor protein p62 markedly increases p62's binding affinity for Keap1, an adaptor of the Cul3-ubiquitin E3 ligase complex responsible for degrading Nrf2, and that inhibitors of the interaction between phosphorylated p62 and Keap 1 have potential as therapeutic agents against human HCC.

TL;DR: This work identifies a cell cycle-regulated circuit, underpinned by RIF1 and BRCA1, that governs DSB repair pathway choice to ensure that NHEJ dominates in G1 and HR is favored from S phase onward.

TL;DR: The crystal structure of STING bound to 2'3'-cGAMP revealed the structural basis of this high-affinity binding and a ligand-induced conformational change in STING that may underlie its activation, and showed that endogenous cGAMP in mammalian cells contains two distinct phosphodiester linkages.

TL;DR: Systematic profiling of the mammalian succinylome reveals widespread roles for lysine succinylation in regulating metabolism and potentially other cellular functions, and identifies two protein complexes identified in the analysis.

TL;DR: The experimental and theoretical data on this hierarchy of structures and a key role for the recently discovered topologically associating domains are reviewed and proposed.

TL;DR: The stage is now set to reveal fundamental epigenetic mechanisms that determine how Polycomb target genes are silenced and howPolycomb silence is preserved through cell-cycle progression.

TL;DR: Rif1−/− mice are severely compromised for 53BP1-dependent class switch recombination (CSR) and fusion of dysfunctional telomeres and deletion of Rif1 suppresses toxic nonhomologous end joining (NHEJ) induced by PARP inhibition in Brca1-deficient cells.

TL;DR: An essential role of enhancer transcription in H3K4me1/2 deposition at de novo enhancers that is independent of potential functions of the resulting eRNA transcripts is suggested.

TL;DR: This work developed and applied a quantitative mass spectrometry method to probe the liver mitochondrial acetyl-proteome during CR versus control diet in mice that were wild-type or lacked the protein deacetylase SIRT3, and revealed widespread reprogramming of mitochondrial protein acetylation in response to CR.

TL;DR: It is shown that the activation of NLRP3 inflammasome is regulated by a deubiquitination mechanism, and the deubiqueitinating enzyme, BRCC3, is identified as a critical regulator ofNLRP3 activity by promoting its deubanquitination and characterizing NLRP 3 as a substrate for the cytosolic BRCC 3-containing BRISC complex.

TL;DR: Research that has revealed how ubiquitylation and sumoylation regulate and coordinate various pathways of DNA damage recognition, signaling, and repair at the biochemical, cellular, and whole-organism levels is reviewed.

TL;DR: The glucose influx through GLUT1 restores ATP-to-ADP ratios in the short run and ultimately induces TXNIP protein production to suppress glucose uptake once energy homeostasis is reestablished.

TL;DR: This work ascribes transcription enhancement activity to p53 with the capacity to regulate multiple genes from a single genomic binding site and produces enhancer RNAs that are required for efficient transcriptional enhancement of interacting target genes and induction of a p53-dependent cell-cycle arrest.

TL;DR: The role of the RGG/RG motif in mediating nucleic acid and protein interactions, a function that is often regulated by arginine methylation and partner-binding proteins, is discussed.

TL;DR: Continuous response curves measured in multiple cell lines reveal that proliferation is effectively silenced only when ERK pathway output falls below a threshold of ~10%, indicating that high-dose targeting of the pathway is necessary to achieve therapeutic efficacy.

TL;DR: It is found that the lncRNA Low Expression in Tumor (lncRNA-LET) was generally downregulated in hepatocellular carcinomas, colorectal cancers, and squamous-cell lung carcinomas and the downregulation was found to be a key step in the stabilization of nuclear factor 90 protein, which leads to hypoxia-induced cancer cell invasion.

TL;DR: In this paper, it was shown that RagC/D is a key regulator of the interaction of mTORC1 with the Rag heterodimer and that, unexpectedly, RagC and D must be GDP bound for the interaction to occur.

TL;DR: The data suggest that eRNAs contribute to establishing a cell-type-specific transcriptional circuitry by directing chromatin-remodeling events by regulating genomic access of the transcriptional complex to defined regulatory regions.

TL;DR: EIF5A, like its bacterial ortholog EFP, is proposed to stimulate the peptidyl transferase activity of the ribosome and facilitate the reactivity of poor substrates like Pro.

TL;DR: It is concluded that human cells adopt unique strategies and recruit distinct trans-acting factors to carry out essential processing steps, posing fundamental implications for understanding ribosomopathies at the molecular level and developing effective therapeutic agents.

TL;DR: The role of RMST is established as a transcriptional coregulator of SOX2 and a key player in the regulation of neural stem cell fate and a large pool of downstream genes implicated in neurogenesis.

TL;DR: It is found that most acetylation occurred at a low level and accumulated in growth-arrested cells in a manner that depended on the formation of acetyl-phosphate (AcP) through glycolysis, suggesting that AcP may acetylate proteins nonenzymatically in cells.

TL;DR: It is shown that Fbxl10 interacts with Ring1B and Nspc1, forming a noncanonical PRC1 that is required for H2AK119ub1 in mouse ESCs and has a key role in regulating Ring1 B recruitment to its target genes and H2 AK119 ubiquitylation in ESCs.

TL;DR: Developments discussed in this Perspective will soon enable complete proteome analysis of mammalian cells, as well, with profound impact on biology and biomedicine.

TL;DR: It is shown that the transcription factor A-MYB initiates pachytene piRNA production and regulation of piRNA pathway proteins and piRNA genes creates a coherent feedforward loop that ensures the robust accumulation of pachyTene piRNAs.