Objective Eukaryotic translation is mainly controlled at the initiation level. The nature of the 5'- and 3'- non-coding sequences (leaders and trailers, including polyA-tails) and a set of translation initiation factors are the major determinants of this control. Normally translation initiation consists of three stages: cap recognition, scanning to find an appropriate start codon, formation of the 80S ribosome. Each step is characterized by certain initiation factors. Major variations of this standard mechanism exist and those have been mainly studied with virus genomes. These variations offer a possibility of control, e.g. by heat shock, virus infection, starvation. All of the member groups of the project have made important contributions to the field.The studies proposed here aim to determine: the general conditions and types of RNAs that make the cap dispensable; the role of small open reading frames (sORFs) and structural elements within the leader, which either affect translation as such or in the form of an RNA-protein complex; the nature of non-linear scanning to allow a bypass (shunting) of inhibiting elements; and to understand mechanisms of internal initiation.Furthermore, the role of the ribosomal subunits and their modification after heat shock, especially in respect to ribosomal RNAs will be analysed. The initiation factors and conditions involved in using these translational control elements should be specified further. The applicants like to learn more about the role and the interplay of classical eukaryotic initiation factors (eIF) and also non-classical ones, such as the cauliflower mosaic virus translation transactivator. The effect of heat shock on translation and structure of the ribosome, especially the role of a small ribosomal RNA that is created upon heat shock and its affinity for eIF2 will be studied, as well as on the stringency of cap-requirement. Using animal and yeast systems will test the universality of RNA-based translational enhancers found in plant. Knowledge gained and sequences determined will be used for the construction of DNA vectors allowing high level of translation of payload genes and polycistronic translation in vitro and also to construct expression cassettes to be used as transgenes for efficient and polycistronic translation in plants.Results will shade light on the basic mechanisms of cap recognition, initiation complex formation, mechanism of scanning, and the role of sORFs in controlling translation.The applicants together have a wide range of know-how covering the field and complement each other well in their experience with various technologies. The project is expected to lead to interesting publications and applications that could be patented. Scientific exchange will be guarantied by mutual visits of INTAS members to the NIS labs for several months, by meeting at international conferences and through an E-mail network. Programme(s) IC-INTAS - International Association for the promotion of cooperation with scientists from the independent states of the former Soviet Union (INTAS), 1993- Topic(s) 4 - Life Sciences OPEN - OPEN Call Call for proposal Data not available Funding Scheme Data not available Coordinator Friedrich-Miescher-Institute EU contribution No data Address Maulbeerstr. 66 4058 Basel Switzerland See on map Total cost No data Participants (4) Sort alphabetically Sort by EU Contribution Expand all Collapse all EMBL Germany EU contribution No data Address Meyerhofstrasse 1 69117 Heidelberg See on map Total cost No data Kazakh National Center of Biotechnology KNCB Kazakhstan EU contribution No data Address Dosmukhamedov Street, 86 480012 Almaty See on map Total cost No data M.V. Lomonosov Moscow State University Russia EU contribution No data Address Vorobjevy Gori 119899 Moscow See on map Total cost No data Russian Academy of Sciences Russia EU contribution No data Address Institute Street 142292 Pushchino, Moscow Region See on map Total cost No data
