3,414 research outputs found
Writing a wrong: Coupled RNA polymerase II transcription and RNA quality control
Processing and maturation of precursor RNA species is coupled to RNA polymerase II transcription. Co-transcriptional RNA processing helps to ensure efficient and proper capping, splicing, and 3' end processing of different RNA species to help ensure quality control of the transcriptome. Many improperly processed transcripts are not exported from the nucleus, are restricted to the site of transcription, and are in some cases degraded, which helps to limit any possibility of aberrant RNA causing harm to cellular health. These critical quality control pathways are regulated by the highly dynamic protein-protein interaction network at the site of transcription. Recent work has further revealed the extent to which the processes of transcription and RNA processing and quality control are integrated, and how critically their coupling relies upon the dynamic protein interactions that take place co-transcriptionally. This review focuses specifically on the intricate balance between 3' end processing and RNA decay during transcription termination. This article is categorized under: RNA Turnover and Surveillance > Turnover/Surveillance Mechanisms RNA Processing > 3' End Processing RNA Processing > Splicing Mechanisms RNA Processing > Capping and 5' End Modifications
District Workforce Development and Instructional Capacity: A Strategic Perspective
Paper presented at the annual American Educational Research Association Conference,
New York City, New York, March 24-28, 2008.Some depictions of human resource (HR) functions tend to see connections to core missions, e.g., teaching and learning, as a
“hub and spoke” arrangement with HR functions such as recruitment, selection,
induction, professional development, and so on. Clearly, the gap between strategic
intentions and practice is a challenge across public and private sectors and across
3 industries. We also suspect that the lack of evidence of strategic practice in school
districts may have something to do with limited conceptualizations of strategic human
resource management (SHRM) that could otherwise lead to observations from which
theorizing and evaluation can take place
Accessing the purity of a single photon by the width of the Hong-Ou-Mandel interference
We demonstrate a method to determine the spectral purity of single photons.
The technique is based on the Hong-Ou-Mandel (HOM) interference between a
single photon state and a suitably prepared coherent field. We show that the
temporal width of the HOM dip is not only related to reciprocal of the spectral
width but also to the underlying quantum coherence. Therefore, by measuring the
width of both the HOM dip and the spectrum one can directly quantify the degree
of spectral purity. The distinct advantage of our proposal is that it obviates
the need for perfect mode matching, since it does not rely on the visibility of
the interference. Our method is particularly useful for characterizing the
purity of heralded single photon states.Comment: Extended version, 16 pages, 9 figure
Expert advice and political choice in constructing European banking union
International actors promoted the transfer of regulatory authority and financial resources from national governments to the European Union (EU) in the context of establishing the prerequisites for financial stability in Europe through banking union. It was supplied, however, by a political process that kept significant resources in resolution and deposit insurance largely in national hands. This article examines the politics behind those decisions, and how the hybrid of European and national competences affects bank regulation and financial stability in the EU. It concludes that the tension between strong EU supervisory powers and weak capacity to deal with insolvent institutions will persist
Rtr1 is a dual specificity phosphatase that dephosphorylates Tyr1 and Ser5 on the RNA Polymerase II CTD
The phosphorylation state of heptapeptide repeats within the C-terminal domain (CTD) of the largest subunit of RNA Polymerase II (PolII) controls the transcription cycle and is maintained by the competing action of kinases and phosphatases. Rtr1 was recently proposed to be the enzyme responsible for the transition of PolII into the elongation and termination phases of transcription by removing the phosphate marker on Serine 5, but this attribution was questioned by the apparent lack of enzymatic activity. Here we demonstrate that Rtr1 is a phosphatase of new structure that is auto-inhibited by its own C-terminus. The enzymatic activity of the protein in vitro is functionally important in vivo as well: a single amino acid mutation that reduces activity leads to the same phenotype in vivo as deletion of the protein-coding gene from yeast. Surprisingly, Rtr1 dephosphorylates not only Serine 5 on the CTD, but also the newly described anti-termination Tyrosine 1 marker, supporting the hypothesis that Rtr1 and its homologs promote the transition from transcription to termination
The Exosome Component Rrp6 Is Required for RNA Polymerase II Termination at Specific Targets of the Nrd1-Nab3 Pathway
Publisher’s version made available under a Creative Commons license.The exosome and its nuclear specific subunit Rrp6 form a 3'-5' exonuclease complex that regulates diverse aspects of RNA biology including 3' end processing and degradation of a variety of noncoding RNAs (ncRNAs) and unstable transcripts. Known targets of the nuclear exosome include short (<1000 bp) RNAPII transcripts such as small noncoding RNAs (snRNAs), cryptic unstable transcripts (CUTs), and some stable unannotated transcripts (SUTs) that are terminated by an Nrd1, Nab3, and Sen1 (NNS) dependent mechanism. NNS-dependent termination is coupled to RNA 3' end processing and/or degradation by the Rrp6/exosome in yeast. Recent work suggests Nrd1 is necessary for transcriptome surveillance, regulating promoter directionality and suppressing antisense transcription independently of, or prior to, Rrp6 activity. It remains unclear whether Rrp6 is directly involved in termination; however, Rrp6 has been implicated in the 3' end processing and degradation of ncRNA transcripts including CUTs. To determine the role of Rrp6 in NNS termination globally, we performed RNA sequencing (RNA-Seq) on total RNA and perform ChIP-exo analysis of RNA Polymerase II (RNAPII) localization. Deletion of RRP6 promotes hyper-elongation of multiple NNS-dependent transcripts resulting from both improperly processed 3' RNA ends and faulty transcript termination at specific target genes. The defects in RNAPII termination cause transcriptome-wide changes in mRNA expression through transcription interference and/or antisense repression, similar to previously reported effects of depleting Nrd1 from the nucleus. Elongated transcripts were identified within all classes of known NNS targets with the largest changes in transcription termination occurring at CUTs. Interestingly, the extended transcripts that we have detected in our studies show remarkable similarity to Nrd1-unterminated transcripts at many locations, suggesting that Rrp6 acts with the NNS complex globally to promote transcription termination in addition to 3' end RNA processing and/or degradation at specific targets
Avulsion cycles and their stratigraphic signature on an experimental backwater‐controlled delta
River deltas grow in large part through repeated cycles of lobe construction and channel avulsion. Understanding avulsion cycles is important for coastal restoration and ecology, land management, and flood hazard mitigation. Emerging theories suggest that river avulsions on lowland deltas are controlled by backwater hydrodynamics; however, our knowledge of backwater-controlled avulsion cycles is limited. Here, we present results from an experimental delta that evolved under persistent backwater hydrodynamics achieved through variable flood discharges, shallow bed-slopes, and subcritical flows. The experimental avulsion cycles consisted of an initial phase of avulsion setup, an avulsion trigger, selection of a new flow path, and abandonment of the parent channel. Avulsions were triggered during the largest floods (78% of avulsions) after the channel was filled by a fraction (0.3 ± 0.13) of its characteristic flow depth at the avulsion site, which occurred in the upstream part of the backwater zone. The new flow path following avulsion was consistently one of the shortest paths to the shoreline, and channel abandonment occurred through temporal decline in water flow and sediment delivery to the parent channel. Experimental synthetic stratigraphy indicates that the bed thicknesses were maximum at the avulsion sites, consistent with our morphologic measurements of avulsion setup and the idea that there is a record of avulsion locations and thresholds in sedimentary rocks. Finally, we discuss the implications of our findings within the context of sustainable management of deltas, their stratigraphic record, and predicting avulsions on deltas
Transcriptional Activity of the Islet β Cell Factor Pdx1 is Augmented by Lysine Methylation Catalyzed by the Methyltransferase Set7/9
The transcription factor Pdx1 is crucial to islet β cell function and regulates target genes in part through interaction with coregulatory factors. Set7/9 is a Lys methyltransferase that interacts with Pdx1. Here we tested the hypothesis that Lys methylation of Pdx1 by Set7/9 augments Pdx1 transcriptional activity. Using mass spectrometry and mutational analysis of purified proteins, we found that Set7/9 methylates the N-terminal residues Lys-123 and Lys-131 of Pdx1. Methylation of these residues occurred only in the context of intact, full-length Pdx1, suggesting a specific requirement of secondary and/or tertiary structural elements for catalysis by Set7/9. Immunoprecipitation assays and mass spectrometric analysis using β cells verified Lys methylation of endogenous Pdx1. Cell-based luciferase reporter assays using wild-type and mutant transgenes revealed a requirement of Pdx1 residue Lys-131, but not Lys-123, for transcriptional augmentation by Set7/9. Lys-131 was not required for high-affinity interactions with DNA in vitro, suggesting that its methylation likely enhances post-DNA binding events. To define the role of Set7/9 in β cell function, we generated mutant mice in which the gene encoding Set7/9 was conditionally deleted in β cells (SetΔβ). SetΔβ mice exhibited glucose intolerance similar to Pdx1-deficient mice, and their isolated islets showed impaired glucose-stimulated insulin secretion with reductions in expression of Pdx1 target genes. Our results suggest a previously unappreciated role for Set7/9-mediated methylation in the maintenance of Pdx1 activity and β cell function
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