Common conformational changes induced in type 2 picornavirus IRESs by cognate trans-acting factors

Type 2 internal ribosomal entry sites (IRESs) of encephalomyocarditis virus (EMCV), foot-and-mouth disease virus (FMDV) and other picornaviruses comprise five major domains H-L. Initiation of translation on these IRESs begins with specific binding of the central domain of initiation factor, eIF4G to the J-K domains, which is stimulated by eIF4A. eIF4G/eIF4A then restructure the region of ribosomal attachment on the IRES and promote recruitment of ribosomal 43S pre-initiation complexes. In addition to canonical translation factors, type 2 IRESs also require IRES trans-acting factors (ITAFs) that are hypothesized to stabilize the optimal IRES conformation that supports efficient ribosomal recruitment: the EMCV IRES is stimulated by pyrimidine tract binding protein (PTB), whereas the FMDV IRES requires PTB and ITAF45. To test this hypothesis, we assessed the effect of ITAFs on the conformations of EMCV and FMDV IRESs by comparing their influence on hydroxyl radical cleavage of these IRESs from the central domain of eIF4G. The observed changes in cleavage patterns suggest that cognate ITAFs promote similar conformational changes that are consistent with adoption by the IRESs of comparable, more compact structures, in which domain J undergoes local conformational changes and is brought into closer proximity to the base of domain I

Involvement of yeast HSP90 isoforms in response to stress and cell death induced by acetic acid

Acetic acid-induced apoptosis in yeast is accompanied by an impairment of the general protein synthesis machinery, yet paradoxically also by the up-regulation of the two isoforms of the heat shock protein 90 (HSP90) chaperone family, Hsc82p and Hsp82p. Herein, we show that impairment of cap-dependent translation initiation induced by acetic acid is caused by the phosphorylation and inactivation of eIF2 alpha by Gcn2p kinase. A microarray analysis of polysome-associated mRNAs engaged in translation in acetic acid challenged cells further revealed that HSP90 mRNAs are over-represented in this polysome fraction suggesting preferential translation of HSP90 upon acetic acid treatment. The relevance of HSP90 isoform translation during programmed cell death (PCD) was unveiled using genetic and pharmacological abrogation of HSP90, which suggests opposing roles for HSP90 isoforms in cell survival and death. Hsc82p appears to promote survival and its deletion leads to necrotic cell death, while Hsp82p is a pro-death molecule involved in acetic acid-induced apoptosis. Therefore, HSP90 isoforms have distinct roles in the control of cell fate during PCD and their selective translation regulates cellular response to acetic acid stress.This work was supported by Fundacao para a Ciencia e Tecnologia and COMPETE/QREN/EU (PTDC/BIA-MIC/114116/2009), and by the Canadian Institute for Health Research (MOP 89737 to MH). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript

The Polycomb Protein and E3 Ubiquitin Ligase Ring1B Harbors an IRES in its Highly Conserved 5′ UTR

Ring1B is an essential member of the highly conserved Polycomb group proteins, which orchestrate developmental processes, cell growth and stem cell fate by modifying local chromatin structure. Ring1B was found to be the E3 ligase that monoubiquitinates histone H2A, which adds a new level of chromatin modification to Polycomb group proteins. Here we report that Ring1B belongs to the exclusive group of proteins that for their translation depend on a stable 5′ UTR sequence in their mRNA known as an Internal Ribosome Entry Site (IRES). In cell transfection assays the Ring1B IRES confers significantly higher expression levels of Ring1B than a Ring1B cDNA without the IRES. Also, dual luciferase assays show strong activity of the Ring1B IRES. Although our findings indicate Ring1B can be translated under conditions where cap-dependent translation is impaired, we found the Ring1B IRES to be cap-dependent. This raises the possibility that translational control of Ring1B is a multi-layered process and that translation of Ring1B needs to be maintained under varying conditions, which is in line with its essential role as an E3 ligase for monoubiquitination of histone H2A in the PRC1 Polycomb protein complex

Measurement of single-diffractive dijet production in proton-proton collisions at root s=8 TeV with the CMS and TOTEM experiments

A Publisher's Erratum to this article was published on 03 May 2021. https://doi.org/10.1140/epjc/s10052-021-08863-wPeer reviewe

Observation of proton-tagged, central (semi)exclusive production of high-mass lepton pairs in pp collisions at 13 TeV with the CMS-TOTEM precision proton spectrometer

The process pp -> pl(+)l(-)p(()*()), with l(+)l(-) a muon or an electron pair produced at midrapidity with mass larger than 110 GeV, has been observed for the first time at the LHC in pp collisions at root s = 13 TeV. One of the two scattered protons is measured in the CMS-TOTEM precision proton spectrometer (CT-PPS), which operated for the first time in 2016. The second proton either remains intact or is excited and then dissociates into a low-mass state p*, which is undetected. The measurement is based on an integrated luminosity of 9.4 fb(-1) collected during standard, high-luminosity LHC operation. A total of 12 mu(+)/mu(-) and 8 e(+)e(-) pairs with m(l(+)l(-)) > 110 GeV, and matching forward proton kinematics, are observed, with expected backgrounds of 1.49 +/- 0.07 (stat) +/- 0.53 (syst) and 2.36 +/- 0.09 (stat) +/- 0.47(syst), respectively. This corresponds to an excess of more than five standard deviations over the expected background. The present result constitutes the first observation of proton-tagged gamma gamma collisions at the electroweak scale. This measurement also demonstrates that CT-PPS performs according to the design specifications.Peer reviewe

Search for MSSM Higgs bosons decaying to mu(+)mu(-) in proton-proton collisions at root s=13TeV

A search is performed for neutral non-standard-model Higgs bosons decaying to two muons in the context of the minimal supersymmetric standard model (MSSM). Proton-proton collision data recorded by the CMS experiment at the CERN Large Hadron Collider at a center-of-mass energy of 13 TeV were used, corresponding to an integrated luminosity of 35.9 fb(-1). The search is sensitive to neutral Higgs bosons produced via the gluon fusion process or in association with a b (b) over bar quark pair. No significant deviations from the standard model expectation are observed. Upper limits at 95% confidence level are set in the context of the m(h)(mod+) and phenomenological MSSM scenarios on the parameter tan beta as a function of the mass of the pseudoscalar A boson, in the range from 130 to 600 GeV. The results are also used to set a model-independent limit on the product of the branching fraction for the decay into a muon pair and the cross section for the production of a scalar neutral boson, either via gluon fusion, or in association with b quarks, in the mass range from 130 to 1000 GeV. (C) 2019 The Author(s). Published by Elsevier B.V

Search for resonances decaying to a pair of Higgs bosons in the bb̅qq̅’ℓν final state in proton-proton collisions at √s = 13 TeV

A search for new massive particles decaying into a pair of Higgs bosons in proton-proton collisions at a center-of-mass energy of 13 TeV is presented. Data were collected with the CMS detector at the LHC, corresponding to an integrated luminosity of 35.9 fb⁻¹. The search is performed for resonances with a mass between 0.8 and 3.5 TeV using events in which one Higgs boson decays into a bottom quark pair and the other decays into two W bosons that subsequently decay into a lepton, a neutrino, and a quark pair. The Higgs boson decays are reconstructed with techniques that identify final state quarks as substructure within boosted jets. The data are consistent with standard model expectations. Exclusion limits are placed on the product of the cross section and branching fraction for generic spin-0 and spin-2 massive resonances. The results are interpreted in the context of radion and bulk graviton production in models with a warped extra spatial dimension. These are the best results to date from searches for an HH resonance decaying to this final state, and they are comparable to the results from searches in other channels for resonances with masses below 1.5 TeV

Production of Lambda(+)(c) baryons in proton-proton and lead-lead collisions at root S-NN=5.02 TeV

The transverse momentum (P-T) spectra of inclusively produced A c P baryons are measured via the exclusive decay channel Lambda(+)(c) -> pK(-)pi(+) using the CMS detector at the LHC. Spectra are measured as a function of transverse momentum in proton-proton (pp) and lead-lead (PbPb) collisions at a nucleonnucleon center-of-mass energy of 5.02TeV. The measurement is performed within the Lambda(+)(c) rapidity interval vertical bar Y vertical bar <1 in the p(T) range of 5-20GeV/c in pp and 10-20GeV/c in PbPb collisions. The observed yields of Lambda(+)(c) for p(T) of 10-20 GeV/c suggest a suppression in central PbPb collisions compared to pp collisions scaled by the number of nucleon-nucleon (NN) interactions. The Lambda(+)(c)/D-0 production ratio in pp collisions is compared to theoretical models. In PbPb collisions, this ratio is consistent with the result from pp collisions in their common p-r range. (C) 2020 The Author(s). Published by Elsevier B.V.Peer reviewe