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Translation initiation is a complex process in which initiator tRNA, 40S, and 60S ribosomal subunits are assembled by eukaryotic initiation factors (eIFs) into an 80S ribosome at the initiation codon of mRNA. The cap-binding complex eIF4F and the factors eIF4A and eIF4B are required for binding of 43S complexes (comprising a 40S subunit, eIF2/GTP/Met-tRNAi(More)
Cap-independent translation initiation on picornavirus mRNAs is mediated by an internal ribosomal entry site (IRES) in the 5' untranslated region (5' UTR) and requires both eukaryotic initiation factors (eIFs) and IRES-specific cellular trans-acting factors (ITAFs). We show here that the requirements for trans-acting factors differ between related(More)
Heat causes protein misfolding and aggregation and, in eukaryotic cells, triggers aggregation of proteins and RNA into stress granules. We have carried out extensive proteomic studies to quantify heat-triggered aggregation and subsequent disaggregation in budding yeast, identifying >170 endogenous proteins aggregating within minutes of heat shock in(More)
A model of secondary structure common for the central part (ca. 400 nucleotides) of the 5'-untranslated regions (5'-UTR) of all the so far sequenced genomes of polioviruses, coxsackieviruses, and rhinoviruses was derived on the basis of evolutionary and thermodynamic considerations. According to the model, this part of the genome comprises three domains,(More)
The key steps in the replication of the poliovirus genome, initiation of (-) and (+) strands, require two different cis-acting elements, oriR and oriL, respectively. It has been proposed that the spatial organization of these elements is maintained by tertiary ('kissing') interactions between the loops of two constituent hairpins. Here, the putative(More)
The critical role of the ubiquitin-26S proteasome system in regulation of protein homeostasis in eukaryotes is well established. In contrast, the impact of the ubiquitin-independent proteolytic activity of proteasomes is poorly understood. Through biochemical analysis of mammalian lysates, we find that the 20S proteasome, latent in peptide hydrolysis,(More)
Initiation of translation on picornaviral RNA templates occurs via cap-independent ribosome binding to a cis-acting element, internal ribosome entry site (IRES). Mapping of the starting point of translation relative to the IRES was attempted using Theiler's murine encephalomyelitis virus (TMEV) RNA as a model. The possibility that the starting point is(More)
Initiation of translation on picornavirus RNAs is accomplished through internal binding of ribosomes to a complex cis-acting element. Here we show that efficient function of this element involves two appropriately spaced smaller elements: UUUCC and an AUG. This conclusion emerged from analysis of the genome structures of spontaneous revertants of mutant(More)
On the basis of a comparative analysis of published sequences, models for the secondary structure of the 3'-terminal [poly(A)-preceding] untranslated region of the entero- and rhinovirus RNAs were worked out. The models for all these viruses share a common core element, but there are an extra enterovirus-specific element and still an additional element(More)
Higher-order RNA structures in the 3' untranslated region (3'UTR) of enteroviruses are thought to play a pivotal role in viral negative-strand RNA synthesis. The structure of the 3'UTR was predicted by thermodynamic calculations using the STAR (structural analysis of RNA) computer program and experimentally verified using chemical and enzymatic probing of(More)