Alternate Conformations Regulate Ribosomal Recoding in a Positive-sense RNA Virus

Positive-sense RNA viruses are important animal, plant, insect and bacteria pathogens and constitute the largest group of RNA viruses. Due to the relatively small size of their genomes, these viruses have evolved a variety of non-canonical translation mechanisms to optimize coding capacity expanding their proteome diversity. One such strategy is codon redefinition or recoding. First described in viruses, recoding is a programmed translation event in which codon alterations are context dependent. Recoding takes place in a subset of messenger RNA (mRNAs) with some products reflecting new, and some reflecting standard, meanings. The ratio between the two is both critical and highly regulated. While a variety of recoding mechanisms have been documented, (ribosome shunting, stop-carry on, termination-reinitiation, and translational bypassing), the two most extensively employed by RNA viruses are Programmed Ribosomal Frameshifting (PRF) and Programmed Ribosomal Readthrough (PRT). While both PRT and PRF subvert normal decoding for expression of C-terminal extension products, the former involves an alteration of reading frame, and the latter requires decoding of a non-sense codon. Both processes occur at a low but defined frequency, and both require Recoding Stimulatory Elements (RSE) for regulation and optimum functionality. These stimulatory signals can be embedded in the RNA in the form of sequence or secondary structure, or trans-acting factors outside the mRNA such as proteins or micro RNAs (miRNA). Despite 40+ years of study, the precise mechanisms by which viral RSE mediate ribosome recoding for the synthesis of their proteins, or how the ratio of these products is maintained, is poorly defined. This study reveals that in addition to a long distance RNA:RNA interaction, three alternate conformations and a phylogenetically conserved pseudoknot regulate PRT in the carmovirus Turnip crinkle virus (TCV).

Turkish Security Policymaking on Nuclear Issues: Conceptualizing Advanced Cooperative Security Strategies

Turkey is a non-nuclear member of a nuclear alliance in a region where nuclear proliferation is of particular concern. As the only North Atlantic Treaty Organization (NATO) member that has a border with the Middle East, Turkish officials argue that Turkey cannot solely rely on NATO guarantees in addressing the regional security challenges. However, Turkey has not been able to formulate a security policy that reconciles its quest for independence, its NATO membership, the bilateral relationship with the United States, and regional engagement in the Middle East. This dissertation assesses the strategic implications of Turkey’s perceptions of the U.S./NATO nuclear and conventional deterrence on nuclear issues. It explores three case studies by the process tracing of Turkish policymakers’ nuclear-related decisions on U.S. tactical nuclear weapons deployed in Europe, national air and missile defense, and Iran’s nuclear program. The study finds that the principles of Turkish security policymaking do not incorporate a fundamentally different reasoning on nuclear issues than conventional deterrence. Nuclear weapons and their delivery systems do not have a defining role in Turkish security and defense strategy. The decisions are mainly guided by non-nuclear considerations such as Alliance politics, modernization of the domestic defense industry, and regional influence. The dissertation argues that Turkey could formulate more effective and less risky security policies on nuclear issues by emphasizing the cooperative security approaches within the NATO Alliance over confrontational measures. The findings of this dissertation reveal that a major transformation of Turkish security policymaking is required to end the crisis of confidence with NATO, redefinition of the strategic partnership with the US, and a more cautious approach toward the Middle East. The dissertation argues that Turkey should promote proactive measures to reduce, contain, and counter risks before they develop into real threats, as well as contribute to developing consensual confidence-building measures to reduce uncertainty.