Functional interplay between DEAD-box RNA helicases Ded1 and Dbp1 in preinitiation complex attachment and scanning on structured mRNAs in vivo

RNA structures that impede ribosome binding or subsequent scanning of the 5′-untranslated region (5′-UTR) for the AUG initiation codon reduce translation efficiency. Yeast DEAD-box RNA helicase Ded1 appears to promote translation by resolving 5′-UTR structures, but whether its paralog, Dbp1, performs similar functions is unknown. Furthermore, direct in vivo evidence was lacking that Ded1 or Dbp1 resolves 5′-UTR structures that impede attachment of the 43S preinitiation complex (PIC) or scanning. Here, profiling of translating 80S ribosomes reveals that the translational efficiencies of many more mRNAs are reduced in a ded1-ts dbp1Δ double mutant versus either single mutant, becoming highly dependent on Dbp1 or Ded1 only when the other helicase is impaired. Such ‘conditionally hyperdependent’ mRNAs contain unusually long 5′-UTRs with heightened propensity for secondary structure and longer transcript lengths. Consistently, overexpressing Dbp1 in ded1 cells improves the translation of many such Ded1-hyperdependent mRNAs. Importantly, Dbp1 mimics Ded1 in conferring greater acceleration of 48S PIC assembly in a purified system on mRNAs harboring structured 5′-UTRs. Profiling 40S initiation complexes in ded1 and dbp1 mutants provides direct evidence that Ded1 and Dbp1 cooperate to stimulate both PIC attachment and scanning on many Ded1/Dbp1-hyperdependent mRNAs in vivo.Intramural Research Program of the National Institutes of Health; Australian Research Council Discovery Project grant [DP180100111 to T.P.]; National Health and Medical Research Council of Australia Senior Research Fellowship [APP1135928]. Funding for open access charge: Intramural Research Program of the National Institutes of Health

Il concetto di sovranità in Asia Centrale

ISBN (Print): 9788869693779 ISBN (Ebook): 9788869693762This article studies the interpretation and the practice of sovereignty in Central Asia. By relying on primary and secondary research material, the paper intends to achieve three main objectives: 1) to discuss the extent to which ‘sovereignty’ in Central Asia is interpreted and practiced along the lines of Western legal traditions, or rather presents indigenous traits; 2) to understand how authoritarianism impacts on the interpretation and the practice of sovereignty; 3) to assess the presence of a postcolonial narrative of sovereignty in the region, or the lack thereof. These objectives are meant to contribute to the regional agenda of the English School by exploring the polysemy of sovereignty, providing a better understanding of how authoritarianism intermingling with international society while interacting with postcolonial discourses in processes of regionalisation and interaction with global international society.Publisher PDFPeer reviewe

Global landscape of HIV–human protein complexes

Human immunodeficiency virus (HIV) has a small genome and therefore relies heavily on the host cellular machinery to replicate. Identifying which host proteins and complexes come into physical contact with the viral proteins is crucial for a comprehensive understanding of how HIV rewires the host’s cellular machinery during the course of infection. Here we report the use of affinity tagging and purification mass spectrometry(1-3) to determine systematically the physical interactions of all 18 HIV-1 proteins and polyproteins with host proteins in two different human cell lines (HEK293 and Jurkat). Using a quantitative scoring system that we call MiST, we identified with high confidence 497 HIV–human protein–protein interactions involving 435 individual human proteins, with ~40% of the interactions being identified in both cell types. We found that the host proteins hijacked by HIV, especially those found interacting in both cell types, are highly conserved across primates. We uncovered a number of host complexes targeted by viral proteins, including the finding that HIV protease cleaves eIF3d, a subunit of eukaryotic translation initiation factor 3. This host protein is one of eleven identified in this analysis that act to inhibit HIV replication. This data set facilitates a more comprehensive and detailed understanding of how the host machinery is manipulated during the course of HIV infection