Showing papers in "Molecular Cell in 2018"

TL;DR: The recent progress on circRNA biogenesis and function is surveyed and technical obstacles in circRNA studies are discussed.

TL;DR: Recent advances into how the UPR integrates information about the intensity and duration of ER stress stimuli in order to control cell fate inform an evolving mechanistic understanding of a wide variety of human diseases, thus opening up the potential for new therapeutic modalities to treat these diverse diseases.

TL;DR: It is demonstrated that Zc3h13 plays a critical role in anchoring WTAP, Virilizer, and Hakai in the nucleus to facilitate m6A methylation and to regulate mESC self-renewal.

TL;DR: Systematic in-vivo proximity-dependent biotinylation analysis of 119 human proteins associated with different aspects of mRNA biology uncovers 7424 unique proximity interactions with 1,792 proteins, which enables the definition of 144 core components of SGs and PBs.

TL;DR: Cicero is introduced, an algorithm that identifies co-accessible pairs of DNA elements using single-cell chromatin accessibility data and so connects regulatory elements to their putative target genes and is applied to investigate how dynamically accessible elements orchestrate gene regulation in differentiating myoblasts.

TL;DR: How multiple levels of regulation shape the conditions of toxin activation to achieve the different biological functions of TA modules is highlighted.

TL;DR: It is shown that metformin increases CTL activity by reducing the stability and membrane localization of programmed death ligand-1 (PD-L1), and it is discovered that AMP-activated protein kinase (AMPK) activated by met formin directly phosphorylates S195 of PD-L 1.

TL;DR: It is demonstrated that the cellular distribution of FTO is distinct among different cell lines, affecting the access of Fto to different RNA substrates, and that FTO can directly repress translation by catalyzing m1A tRNA demethylation.

TL;DR: It is demonstrated that the enrichment of NONO dimers on the redundant NEAT1_2 subdomains initiates construction of phase-separated paraspeckles, providing mechanistic insights into lncRNA-based nuclear body formation.

TL;DR: It is found that keratinocytes and other human cells mount an innate immune response within hours of etoposide-induced DNA damage, which involves the DNA sensing adaptor STING but is independent of the cytosolic DNA receptor cGAS.

TL;DR: The relationship between the chronological and biological clocks, their underlying mechanisms, potential consequences, and their utility as biomarkers and as targets for intervention to promote healthy aging and longevity are considered.

TL;DR: It is shown that 6mA is extensively present in the human genome, and 881,240 6mA sites accounting for ∼0.051% of the total adenines are cataloged, and [G/C]AGG[C/T] was the most significantly associated motif with 6mA modification.

TL;DR: In this article, the affinity landscapes of 78 human RBPs using an unbiased assay that determines the sequence, structure, and context preferences of these proteins in vitro by deep sequencing of bound RNAs.

TL;DR: The small size, minimal targeting constraints, and modular regulation of Cas13d effectors further expands the CRISPR toolkit for RNA-manipulation and detection.

TL;DR: It is discovered that the Target of Rapamycin (TOR) kinase phosphorylates PYL ABA receptors at a conserved serine residue to prevent activation of the stress response in unstressed plants and utilizes this conserved phospho-regulatory feedback mechanism to optimize the balance of growth and stress responses.

TL;DR: The historical milestones from the discovery of the ribosome itself to how this ancient machinery has gained newfound appreciation as a more regulatory participant in the central dogma of gene expression are discussed.

TL;DR: A unified structural view of hnRNPA2 self-assembly, aggregation, and interaction and the distinct effects of small chemical changes-disease mutations and arginine methylation-on these assemblies are provided.

TL;DR: In Drosophila, downregulation of tankyrase, a poly(ADP-ribose) (PAR) polymerase, reduces TDP-43 accumulation in the cytoplasm and potently mitigates neurodegeneration, and small-molecule inhibition of Tankyrase-1/2 in mammalian cells inhibits formation of cy toplasmic T DP-43 foci without affecting stress granule assembly.

TL;DR: The use of ribosome collisions as a proxy for stalling allows the degree of tolerable slowdown to be tuned by the initiation rate on that mRNA; hence, the threshold for triggering quality control is substrate specific.

TL;DR: It is shown that substrates trigger phase separation of SPOP in vitro and co-localization in membraneless organelles in cells and underlies the regulation of ubiquitin-dependent proteostasis.

TL;DR: It is postulate that UBQLN2 LLPS enables its recruitment to stress granules, where its interactions with ubiquitinated substrates reverse LLPS to enable shuttling of clients out of stress granule.

TL;DR: The complexity of the mammalian m7G tRNA methylome is uncovers and its essential role in ESCs with links to human disease is highlighted.

TL;DR: The different chaperone disaggregation machines and their mechanisms of action are reviewed, showing that in all these machines, the coating of protein aggregates by Hsp70 chaperones represents the conserved, initializing step.

TL;DR: It is found that huntingtin exon1 proteins can form reversible liquid-like assemblies, a process driven by huntingtin’s polyQ tract and proline-rich region, and in cells and in vitro, the liquid- like assemblies converted to solid-like assembly with a fibrillar structure.

TL;DR: This work revealed unique features in transcriptional machinery, transcription factor networks, and reciprocal interactions in human oocytes and GCs that displayed developmental-stage-specific expression patterns and identified specific gene signatures of two cell types in particular developmental stage that may reflect developmental competency and ovarian reserve.

TL;DR: The rationale for each step in the UV crosslinking and immunoprecipitation protocol is described and the impact of variations are discussed to help users determine the most suitable option.

TL;DR: The crystal structure of human METTL16 is described to reveal a methyltransferase domain furnished with an extra N-terminal module, which together form a deep-cut groove that is essential for RNA binding.

TL;DR: The data indicate that PARP1 is a sensor of unligated Okazaki fragments during DNA replication and facilitates their repair, and human cells lacking PARP activity and/or XRCC1 are hypersensitive to FEN1 perturbation.

TL;DR: This study revealed the existence of a DSB-induced monoubiquitination-to-acetylation switch on histone H2B lysine 120, likely mediated by the SAGA complex, as well as higher-order signaling at HR-repaired DSBs whereby hist one H1 is evicted while ubiquitin and 53BP1 accumulate over the entire γH2AX domains.

TL;DR: The principles of de novo establishment of PRC2-mediated repressive domains across the genome are demonstrated and shown to be effective at both the cis and far-cis levels.