Translation is the biological process that ultimately leads to the synthesis of a protein from the genetic material mRNA. Protein synthesis is essential for life as we know it, which is rooted in its extreme conservation throughout all living organisms. Translation is typically divided into four phases, the first of which, denominated translation initiation, is the most delicate step, as it entails the determining the correct start site of the produced protein. Previous structural studies allowed us to gain important insights into the position of translation Initiation Factors, and their function during the formation of the bacterial Initiation Complex and the proper positioning of the initiator tRNA on the start codon of the mRNA. Nevertheless, the limited resolution of the structures hampered gaining a pristine view of the molecular details that are essential for the correct assembly of this important step of translation. Moreover, little information is available regarding the differences underlying the initiation of translation on non-canonical start codons. Driven by recent improvements in cryo-EM, this work aims to fill these gaps and shed molecular insights into bacterial initiation of translation. This work further highlights for the first time, at molecular resolution, multiple important interactions that occurs between the 30S subunit, mRNA, initiator tRNA and initiation factors during the process of Initiation Complex formation. Supported by the structural data obtained, a new model for the order of initiation complex assembly is suggested. The model presented underlines the complexity of bacterial initiation of translation and paves the way for future experiments to gain a holistic view of this step of translation.

Poly(A)-binding proteins (PABPs) are important regulators of mRNA translation and stability. In mammals four cytoplasmic PABPs with a similar domain structure have been described - PABP1, tPABP, PABP4 and ePABP. The vast majority of research on PABP mechanism, function and sub-cellular localisation is however limited to PABP1 and little published work has explored the expression of PABP proteins. Here, I examine the tissue distribution of PABP1 and PABP4 in mouse and show that both proteins differ markedly in their expression at both the tissue and cellular level, contradicting the widespread perception that PABP1 is ubiquitously expressed. PABP4 is shown to be widely expressed though with an expression pattern distinct from PABP1, and thus may have a biological function in many tissues. I have shown that PABP4 associates with polysomes and described interactions between PABP4 and proteins important for PABP1-mediated translational activation suggesting that PABP4 plays a similar role in translational regulation. Translational inhibition is a common response to cell stress. Following certain cellular stresses e.g. arsenite, PABP1 localises to cytoplasmic stress granules, sites of mRNA storage. Here, I show that PABP4 is also a component of stress granules and have investigated the role of PABPs in stress granule formation. In contrast, I have shown that both PABP1 and PABP4 relocalise to the nucleus following UV irradiation in both human and mouse cell lines. In order to understand the how the UV-induced change in PABP localisation may be regulated, I have investigated the regulation of PABP nuclear export. I have found that accumulation of PABP proteins in the nucleus after UV coincides with an accumulation of poly(A)+ RNA, indicative of a block in mRNA export, an effect which has not been previously characterized. My working model is that nuclear export of PABPs may be dependent on mRNA export, inhibition of which leads to nuclear accumulation of PABPs after UV, which may in turn augment translational inhibition.

This thesis aims to find a model for translating colloquial registers into Catalan. Colloquial registers play an important part in literature today inasmuch as literature projects real life situations in which informal registers unfold. Many Catalan readers do not have a high regard for Catalan translations because established models for colloquial language do not reflect the way Catalan is spoken today, since there is a divorce between the linguistic norm and oral Catalan as a result of Castilian interference in informal registers. As a consequence, translations tend to be standardised and far from the spontaneous oral Catalan. In order to devise a flexible model for colloquial Catalan in translation, a text which contains a great deal of informal registers has been selected: Hunter S. Thompson’s novel Fear and Loathing in Las Vegas. The analysis of the sociolinguistic situation of the Catalan language and the position of translated literature in the Catalan system allows us to explain why the system is reluctant to change. Norms in the target culture and the principle of equivalence are explored as they prevent translators from shifting towards a model which accommodates Castilian words and expressions. With the aim of explaining why Catalan presents a particular problem in the translation of colloquial language, an analysis of both written and oral texts in English where colloquial registers have been translated into Catalan is carried out. In order to avoid a rigid model which follows the Catalan dictionary and grammar only, features of media oral registers have been applied to the translation of selected fragments of Fear and Loathing in Las Vegas. This allows us to obtain a text which does not include Castilian terms and, at the same time, reproduces a neutral but more realistic colloquial Catalan.

This paper explores the theoretical approaches to translation and the dynamics of language politics during the ʻAbbāsid-era translation movement through the lens of three prominent figures of the ʿAbbāsid era, Ḥunayn ibn Isʹhāq, Mattā bin Yūnus and al-Jāḥiẓ. In conversation with Emily Apter's concept of untranslatability and current concerns about translation into and out of Arabic, this paper examines the cultural implications of claims to translatability and untranslatability. The ʿAbbāsid era presents a particularly useful comparison to the present because rather than being marginal, Arabic was the language of an expanding empire, and also because the ʿAbbāsid era was a kind of 'Golden Age' of translation. The ʿAbbāsid era was an enormously productive period, with translators rendering nearly the entirely corpus of available Greek manuscripts into Arabic. This outpouring of translation activity not only provided an influx of new ideas but provoked a wide-ranging debate among the literati of the time about the possibilities and problems of translation. Examining the figures of al-Jāḥiẓ, Mattā bin Yūnus and Ḥunayn ibn Is'hāq provides a window into this theoretical conversation. Al-Jāḥiẓ, as one of the foremost authorities on Arabic rhetoric, gave voice to more than one view of translation, in part defining Arabic writing as too unique to be translated while elsewhere claiming translations from other languages as the inheritance of the Arab culture. The Aristotelian translator Mattā bin Yūnus provides an example of backlash against translation in which foreign ideas were seen as a threat to Arab identity. Ḥunayn ibn Is'hāq, one of most highly regarded translators of his day, reveals a pragmatic approach to translation which integrated Greek works into Arab society. These three figures reorient the poles of translatability and untranslatability, revealing the potential of both to strengthen hegemony, and show the positive and negative aspects of an Arabocentric and Islamocentric universalism. / text

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During the elongation of the polypeptide chain in eukaryotic protein synthesis, GTP-bound eukaryotic translation elongation factor 1A recruits the aminoacyl tRNA to the A-site of the ribosome. The GDP-GTP recycling is catalysed by the elongation factor 1B complex (eEF1B) which in higher eukaryotes consists of three different subunits: alpha, delta and gamma. Previous studies on eEF1B focused mainly on biochemical analysis and reports of overexpression in tumours and correlation to decreased survival rate but not a lot is known about is biology. The aim of this PhD is to characterise the eEF1B subunits at the molecular level in view of their potential involvement in tumourigenesis using a variety of bioinformatic and laboratory techniques. All three subunits were found to be ubiquitously expressed at mRNA and protein levels in all mouse tissues analysed. In addition, eEF1Bβ has several transcript variants in mice derived from alternative splicing and multiple isoforms, including a brain and testis specific heavier isoform and a muscle-specific form in addition to other forms. The characteristics of each eEF1B subunit were catalogued by further bioinformatic analysis. eEF1Bα was not detectable at early mouse developmental stages, eEF1Bβ showed stronger expression at pre-natal and early post-natal stages than adult stage whereas eEF1Bγ is ubiquitously expressed at similar levels throughout mouse development. In adult mice and human tissues, eEF1B subunits appeared to be expressed in different cell types and cell sub-populations. Surprisingly, cytoplasmic and some nuclear expression was observed in vivo. This nuclear expression pattern could not be observed in cell lines and it was not related to the cell cycle stage in vitro. The expression of eEF1B subunits did not change during the cell cycle except eEF1Bγ which was highly expressed in S-phase arrested cells. Knockdown by siRNAs of eEF1B subunits leads to decreased proliferation, increased number of cells in G0/G1 phase and increase in apoptosis in HeLa, HCT116, DLD1 and HepG2 cells. In contrast, overexpression in HeLa cells with a V5-tagged constructs lead to increased proliferation, increased number of cells in the G2/M phase and increased viability. Knockdown of eEF1Bα and eEF1Bβ leads to a reduction in eEF1Bγ levels; it is therefore possible that the phenotype shown by the knockdown of each subunit individually might be due to the reduced levels of eEF1Bγ. However, overexpression of each subunit did not affect the protein levels of the other subunits. The presence of multiple forms, the complex expression pattern and distribution of each eEF1B subunit in mouse and human tissues, and the knockdown and overexpression effect on cells suggests that the eEF1B complex might have different quaternary forms throughout development and in different cell types, possibly a more intricate role in translation, potential non-canonical functions any of which may be implicated in the potential role of eEF1B subunits in tumourgenesis.