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Abstract Adenosine-to-inosine (A-to-I) RNA editing, catalyzed by ADAR enzymes, is a prevalent and conserved RNA modification. While A-to-I RNA editing is essential in mammals, in Caenorhabditis elegans, it is not, making them invaluable for RNA editing research. In C. elegans, ADR-2 is the sole catalytic A-to-I editing enzyme, and ADR-1 is an RNA editing regulator. ADAR localization is well-studied in humans but not well-established in C. elegans. In this study, we examine the cellular and tissue-specific localization of ADR-2. We show that while ADR-2 is present in most cells in the embryo, at later developmental stages, its expression is both tissue- and cell-type-specific. Additionally, both ADARs are mainly in the nucleus. ADR-2 is adjacent to the chromosomes during the cell cycle. We show that the nuclear localization of endogenous ADR-2 depends on ADBP-1, not ADR-1. In adbp-1 mutant worms, ADR-2 is mislocalized, while ADR-1 is not, leading to decreased editing levels and de-novo editing, mostly in exons, suggesting that ADR-2 is also functional in the cytoplasm. Besides, mutated ADBP-1 affects gene expression. Furthermore, we show that ADR-2 targets adenosines with different surrounding nucleotides in exons and introns. Our findings indicate that ADR-2 cellular localization is highly regulated and affects its function. 

Ubiquitin-like proteins (Ubls) share some features with ubiquitin (Ub) such as their globular 3D structure and the ability to attach covalently to other proteins. Interferon Stimulated Gene 15 (ISG15) is an abundant Ubl that similar to Ub, marks many hundreds of cellular proteins, altering their fate. In contrast to Ub, , ISG15 requires interferon (IFN) induction to conjugate efficiently to other proteins. Moreover, despite the multitude of E3 ligases for Ub-modified targets, a single E3 ligase termed HERC5 (in humans) is responsible for the bulk of ISG15 conjugation. Targets include both viral and cellular proteins spanning an array of cellular compartments and metabolic pathways. So far, no common structural or biochemical feature has been attributed to these diverse substrates, raising questions about how and why they are selected. Conjugation of ISG15 mitigates some viral and bacterial infections and is linked to a lower viral load pointing to the role of ISG15 in the cellular immune response. In an apparent attempt to evade the immune response, some viruses try to interfere with the ISG15 pathway. For example, deconjugation of ISG15 appears to be an approach taken by coronaviruses to interfere with ISG15 conjugates. Specifically, coronaviruses such as SARS-CoV, MERS-CoV, and SARS-CoV-2, encode papain-like proteases (PL1pro) that bear striking structural and catalytic similarities to the catalytic core domain of eukaryotic deubiquitinating enzymes of the Ubiquitin-Specific Protease (USP) sub-family. The cleavage specificity of these PLpro enzymes is for flexible polypeptides containing a consensus sequence (R/K)LXGG, enabling them to function on two seemingly unrelated categories of substrates: (i) the viral polyprotein 1 (PP1a, PP1ab) and (ii) Ub- or ISG15-conjugates. As a result, PLpro enzymes process the viral polyprotein 1 into an array of functional proteins for viral replication (termed non-structural proteins; NSPs), and it can remove Ub or ISG15 units from conjugates. However, by de-conjugating ISG15, the virus also creates free ISG15, which in turn may affect the immune response in two opposite pathways: free ISG15 negatively regulates IFN signaling in humans by binding non-catalytically to USP18, yet at the same time free ISG15 can be secreted from the cell and induce the IFN pathway of the neighboring cells. A deeper understanding of this protein-modification pathway and the mechanisms of the enzymes that counteract it will bring about effective clinical strategies related to viral and bacterial infections 

Measurements are presented of the cross-section for the central exclusive production ofJ/\psi\to\mu^+\mu^- $J/\psi \to {\mu }^{+}{\mu }^{-}$and\psi(2S)\to\mu^+\mu^- $\psi \left(2S\right)\to {\mu }^{+}{\mu }^{-}$processes in proton-proton collisions at\sqrt{s} = 13 \ \mathrm{TeV} $\sqrt{s}=13TeV$with 2016–2018 data. They are performed by requiring both muons to be in the LHCb acceptance (with pseudorapidity2<\eta_{\mu^±} < 4.5 $2<{\eta }_{{\mu }^{\pm }}<4.5$) and mesons in the rapidity range2.0 < y < 4.5 $2.0<y<4.5$. The integrated cross-section results are\sigma_{J/\psi\to\mu^+\mu^-}(2.0 ${\sigma }_{J/\psi \to {\mu }^{+}{\mu }^{-}}(2.0<y_{J/\psi }<4.5,2.0<{\eta }_{{\mu }^{\pm }}<4.5)=400\pm 2\pm 5\pm 12pb,{\sigma }_{\psi \left(2S\right)\to {\mu }^{+}{\mu }^{-}}(2.0<y_{\psi \left(2S\right)}<4.5,2.0<{\eta }_{{\mu }^{\pm }}<4.5)=9.40\pm 0.15\pm 0.13\pm 0.27pb,$where the uncertainties are statistical, systematic and due to the luminosity determination. In addition, a measurement of the ratio of\psi(2S) $\psi \left(2S\right)$andJ/\psi $J/\psi$cross-sections, at an average photon-proton centre-of-mass energy of1\ \mathrm{TeV} $1TeV$, is performed, giving$ = 0.1763 ± 0.0029 ± 0.0008 ± 0.0039,$$ where the first uncertainty is statistical, the second systematic and the third due to the knowledge of the involved branching fractions. For the first time, the dependence of theJ/\psi$ $J/\psi$and\psi(2S) $\psi \left(2S\right)$cross-sections on the total transverse momentum transfer is determined inpp $pp$collisions and is found consistent with the behaviour observed in electron-proton collisions.