Abstract:
:The spliceosome is a complex machine composed of small nuclear ribonucleoproteins (snRNPs) and accessory proteins that excises introns from pre-mRNAs. After assembly the spliceosome is activated for catalysis by rearrangement of subunits to form an active site. How this rearrangement is coordinated is not well-understood. During activation, U4 must be released to allow U6 conformational change, while Prp19 complex (NTC) recruitment is essential for stabilizing the active site. We used multi-wavelength colocalization single molecule spectroscopy to directly observe the key events in Saccharomyces cerevisiae spliceosome activation. Following binding of the U4/U6.U5 tri-snRNP, the spliceosome either reverses assembly by discarding tri-snRNP or proceeds to activation by irreversible U4 loss. The major pathway for NTC recruitment occurs after U4 release. ATP stimulates both the competing U4 release and tri-snRNP discard processes. The data reveal the activation mechanism and show that overall splicing efficiency may be maintained through repeated rounds of disassembly and tri-snRNP reassociation.
journal_name
Elifejournal_title
eLifeauthors
Hoskins AA,Rodgers ML,Friedman LJ,Gelles J,Moore MJdoi
10.7554/eLife.14166subject
Has Abstractpub_date
2016-05-31 00:00:00issn
2050-084Xjournal_volume
5pub_type
杂志文章相关文献
eLife文献大全abstract::Sleep affects brain activity globally, but many cortical sleep waves are spatially confined. Local rhythms serve cortical area-specific sleep needs and functions; however, mechanisms controlling locality are unclear. We identify the thalamic reticular nucleus (TRN) as a source for local, sensory-cortex-specific non-ra...
journal_title:eLife
pub_type: 杂志文章
doi:10.7554/eLife.39111
更新日期:2018-12-25 00:00:00
abstract::In most animals, the brain controls the body via a set of descending neurons (DNs) that traverse the neck. DN activity activates, maintains or modulates locomotion and other behaviors. Individual DNs have been well-studied in species from insects to primates, but little is known about overall connectivity patterns acr...
journal_title:eLife
pub_type: 杂志文章
doi:10.7554/eLife.34272
更新日期:2018-06-26 00:00:00
abstract::Congenital diaphragmatic hernia (CDH) is a severe birth defect. Wt1-null mouse embryos develop CDH but the mechanisms regulated by WT1 are unknown. We have generated a murine model with conditional deletion of WT1 in the lateral plate mesoderm, using the G2 enhancer of the Gata4 gene as a driver. 80% of G2-Gata4(Cre);...
journal_title:eLife
pub_type: 杂志文章
doi:10.7554/eLife.16009
更新日期:2016-09-19 00:00:00
abstract::Using knowledge of the structure of the world to infer value is at the heart of model-based reasoning and relies on a circuit that includes the orbitofrontal cortex (OFC). Some accounts link this to the representation of biological significance or value by neurons in OFC, while other models focus on the representation...
journal_title:eLife
pub_type: 杂志文章
doi:10.7554/eLife.30373
更新日期:2018-03-07 00:00:00
abstract::Over the past century, soybean oil (SBO) consumption in the United States increased dramatically. The main SBO fatty acid, linoleic acid (18:2), inhibits in vitro the growth of lactobacilli, beneficial members of the small intestinal microbiota. Human-associated lactobacilli have declined in prevalence in Western micr...
journal_title:eLife
pub_type: 杂志文章
doi:10.7554/eLife.32581
更新日期:2018-03-27 00:00:00
abstract::RNA molecules cause the proteins involved in the formation of germ granules to coalesce into liquid droplets. ...
journal_title:eLife
pub_type: 评论,杂志文章
doi:10.7554/eLife.24106
更新日期:2017-01-24 00:00:00
abstract::Experience-dependent reorganisation of functional maps in the cerebral cortex is well described in the primary sensory cortices. However, there is relatively little evidence for such cortical reorganisation over the short-term. Using human somatosensory cortex as a model, we investigated the effects of a 24 hr gluing ...
journal_title:eLife
pub_type: 杂志文章
doi:10.7554/eLife.17280
更新日期:2016-12-30 00:00:00
abstract::Intrinsically disordered proteins (IDPs) present a functional paradox because they lack stable tertiary structure, but nonetheless play a central role in signaling, utilizing a process known as allostery. Historically, allostery in structured proteins has been interpreted in terms of propagated structural changes that...
journal_title:eLife
pub_type: 杂志文章
doi:10.7554/eLife.30688
更新日期:2017-10-12 00:00:00
abstract::Duplicating chromosomes once each cell cycle produces sister chromatid pairs, which separate accurately at anaphase. In contrast, reduplicating chromosomes without separation frequently produces polytene chromosomes, a barrier to accurate mitosis. Chromosome reduplication occurs in many contexts, including: polytene t...
journal_title:eLife
pub_type: 杂志文章
doi:10.7554/eLife.15204
更新日期:2016-05-09 00:00:00
abstract::Mitochondria play important roles in cellular processes and disease, yet little is known about how the transcriptional regime of the mitochondrial genome varies across individuals and tissues. By analyzing >11,000 RNA-sequencing libraries across 36 tissue/cell types, we find considerable variation in mitochondrial-enc...
journal_title:eLife
pub_type: 杂志文章
doi:10.7554/eLife.41927
更新日期:2019-02-18 00:00:00
abstract::The basal ganglia are known to be involved in the planning, execution and control of gripping force and movement vigour. Here we aim to define the nature of the basal ganglia control signal for force and to decode gripping force based on local field potential (LFP) activities recorded from the subthalamic nucleus (STN...
journal_title:eLife
pub_type: 杂志文章
doi:10.7554/eLife.19089
更新日期:2016-11-18 00:00:00
abstract::Autophagy has been linked to longevity in many species, but the underlying mechanisms are unclear. Using a GFP-tagged and a new tandem-tagged Atg8/LGG-1 reporter, we quantified autophagic vesicles and performed autophagic flux assays in multiple tissues of wild-type Caenorhabditis elegans and long-lived daf-2/insulin/...
journal_title:eLife
pub_type: 杂志文章
doi:10.7554/eLife.18459
更新日期:2017-07-04 00:00:00
abstract:: ...
journal_title:eLife
pub_type: 杂志文章,已发布勘误
doi:10.7554/eLife.60401
更新日期:2020-06-30 00:00:00
abstract::Increasing evidence highlights the important roles of microRNAs in mediating p53's tumor suppression functions. Here, we report miR-139-5p as another new p53 microRNA target. p53 induced the transcription of miR-139-5p, which in turn suppressed the protein levels of phosphodiesterase 4D (PDE4D), an oncogenic protein i...
journal_title:eLife
pub_type: 杂志文章
doi:10.7554/eLife.15978
更新日期:2016-07-07 00:00:00
abstract::In addition to their role in desensitization and internalization of G protein-coupled receptors (GPCRs), β-arrestins are essential scaffolds linking GPCRs to Erk1/2 signaling. However, their role in GPCR-operated Erk1/2 activation differs between GPCRs and the underlying mechanism remains poorly characterized. Here, w...
journal_title:eLife
pub_type: 杂志文章
doi:10.7554/eLife.23777
更新日期:2017-02-07 00:00:00
abstract::When a plant cell divides, four related proteins control the trafficking of vesicles and ensure that cargo that is normally recycled to the plasma membrane is instead re-routed to the plane of cell division. ...
journal_title:eLife
pub_type: 评论,杂志文章
doi:10.7554/eLife.02747
更新日期:2014-04-08 00:00:00
abstract::Engaging with vocal sounds is critical for children's social-emotional learning, and children with autism spectrum disorder (ASD) often 'tune out' voices in their environment. Little is known regarding the neurobiological basis of voice processing and its link to social impairments in ASD. Here, we perform the first c...
journal_title:eLife
pub_type: 杂志文章
doi:10.7554/eLife.39906
更新日期:2019-02-26 00:00:00
abstract::Postsynaptic compartments can be specifically modulated during various forms of synaptic plasticity, but it is unclear whether this precision is shared at presynaptic terminals. Presynaptic homeostatic plasticity (PHP) stabilizes neurotransmission at the Drosophila neuromuscular junction, where a retrograde enhancemen...
journal_title:eLife
pub_type: 杂志文章
doi:10.7554/eLife.34338
更新日期:2018-04-05 00:00:00
abstract::Rhabdomyosarcoma (RMS) is a pediatric malignacy of muscle with myogenic regulatory transcription factors MYOD and MYF5 being expressed in this disease. Consensus in the field has been that expression of these factors likely reflects the target cell of transformation rather than being required for continued tumor growt...
journal_title:eLife
pub_type: 杂志文章
doi:10.7554/eLife.19214
更新日期:2017-01-12 00:00:00
abstract::Some DNA viruses overcome plant defenses by producing a suppressor protein that blocks the silencing of viral genes. ...
journal_title:eLife
pub_type: 杂志文章
doi:10.7554/eLife.11509
更新日期:2015-10-16 00:00:00
abstract::bicoid mRNA localises to the Drosophila oocyte anterior from stage 9 of oogenesis onwards to provide a local source for Bicoid protein for embryonic patterning. Live imaging at stage 9 reveals that bicoid mRNA particles undergo rapid Dynein-dependent movements near the oocyte anterior, but with no directional bias. Fu...
journal_title:eLife
pub_type: 杂志文章
doi:10.7554/eLife.17537
更新日期:2016-10-28 00:00:00
abstract::Responses of sensory neurons are often modeled using a weighted combination of rectified linear subunits. Since these subunits often cannot be measured directly, a flexible method is needed to infer their properties from the responses of downstream neurons. We present a method for maximum likelihood estimation of subu...
journal_title:eLife
pub_type: 杂志文章
doi:10.7554/eLife.45743
更新日期:2020-03-09 00:00:00
abstract::During mitosis chromosomes reorganise into highly compact, rod-shaped forms, thought to consist of consecutive chromatin loops around a central protein scaffold. Condensin complexes are involved in chromatin compaction, but the contribution of other chromatin proteins, DNA sequence and histone modifications is less un...
journal_title:eLife
pub_type: 杂志文章
doi:10.7554/eLife.57212
更新日期:2020-09-11 00:00:00
abstract::Mating systems have profound effects on genetic diversity and compatibility. The convergent evolution of self-fertilization in three Caenorhabditis species provides a powerful lens to examine causes and consequences of mating system transitions. Among the selfers, Caenorhabditis tropicalis is the least genetically div...
journal_title:eLife
pub_type: 杂志文章
doi:10.7554/eLife.62587
更新日期:2021-01-11 00:00:00
abstract::hIAPP fibrils are associated with Type-II Diabetes, but the link of hIAPP structure to islet cell death remains elusive. Here we observe that hIAPP fibrils are cytotoxic to cultured pancreatic β-cells, leading us to determine the structure and cytotoxicity of protein segments composing the amyloid spine of hIAPP. Usin...
journal_title:eLife
pub_type: 杂志文章
doi:10.7554/eLife.19273
更新日期:2017-01-03 00:00:00
abstract::Genome-wide association studies identified the BIN1 locus as a leading modulator of genetic risk in Alzheimer's disease (AD). One limitation in understanding BIN1's contribution to AD is its unknown function in the brain. AD-associated BIN1 variants are generally noncoding and likely change expression. Here, we determ...
journal_title:eLife
pub_type: 杂志文章
doi:10.7554/eLife.57354
更新日期:2020-07-13 00:00:00
abstract::Kinesin super family protein 2A (KIF2A), an ATP-dependent microtubule (MT) destabilizer, regulates cell migration, axon elongation, and pruning in the developing nervous system. KIF2A mutations have recently been identified in patients with malformed cortical development. However, postnatal KIF2A is continuously expre...
journal_title:eLife
pub_type: 杂志文章
doi:10.7554/eLife.30935
更新日期:2018-01-09 00:00:00
abstract::Dengue Virus (DENV), a flavivirus spread by mosquito vectors, can cause vascular leakage and hemorrhaging. However, the processes that underlie increased vascular permeability and pathological plasma leakage during viral hemorrhagic fevers are largely unknown. Mast cells (MCs) are activated in vivo during DENV infecti...
journal_title:eLife
pub_type: 杂志文章
doi:10.7554/eLife.00481
更新日期:2013-04-30 00:00:00
abstract::Nerve tissue contains a high density of chemical synapses, about 1 per µm3 in the mammalian cerebral cortex. Thus, even for small blocks of nerve tissue, dense connectomic mapping requires the identification of millions to billions of synapses. While the focus of connectomic data analysis has been on neurite reconstru...
journal_title:eLife
pub_type: 杂志文章
doi:10.7554/eLife.26414
更新日期:2017-07-14 00:00:00
abstract::The immediate evolutionary space accessible to HIV is largely determined by how single amino acid mutations affect fitness. These mutational effects can shift as the virus evolves. However, the prevalence of such shifts in mutational effects remains unclear. Here, we quantify the effects on viral growth of all amino a...
journal_title:eLife
pub_type: 杂志文章
doi:10.7554/eLife.34420
更新日期:2018-03-28 00:00:00