The HIV-1 leader RNA conformational switch regulates RNA dimerization but does not regulate mRNA translation
| Autor: | Truus E.M. Abbink, Marcel Ooms, P.C. Joost Haasnoot, Ben Berkhout |
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| Přispěvatelé: | Pediatric surgery, Amsterdam Neuroscience - Cellular & Molecular Mechanisms, Medical Microbiology and Infection Prevention, AII - Amsterdam institute for Infection and Immunity |
| Jazyk: | angličtina |
| Rok vydání: | 2005 |
| Předmět: |
Riboswitch
Genetics Base Sequence Transcription Genetic Molecular Sequence Data Intron RNA Biology Non-coding RNA Stem-loop Biochemistry Small hairpin RNA RNA editing Transcription (biology) Protein Biosynthesis Mutation HIV-1 Nucleic Acid Conformation RNA Viral Thermodynamics RNA Messenger Dimerization |
| Zdroj: | Abbink, T E M, Ooms, M, Haasnoot, P C J & Berkhout, B 2005, ' The HIV-1 leader RNA conformational switch regulates RNA dimerization but does not regulate mRNA translation ', Biochemistry, vol. 44, no. 25, pp. 9058-9066 . https://doi.org/10.1021/bi0502588 Biochemistry, 44(25), 9058-9066. American Chemical Society |
| ISSN: | 0006-2960 |
| DOI: | 10.1021/bi0502588 |
| Popis: | The untranslated leader RNA is the most conserved part of the human immunodeficiency virus type I (HIV-1) genome. It contains many regulatory motifs that mediate a variety of steps in the viral life cycle. Previous work showed that the full-length leader RNA can adopt two alternative structures: a long distance interaction (LDI) and a branched multiple-hairpin (BMH) structure. The BMH structure exposes the dimer initiation site (DIS) hairpin, whereas this motif is occluded in the LDI structure. Consequently, these structures differ in their capacity to form RNA dimers in vitro. The BMH structure is dimerization-competent, due to DIS hairpin formation, but also presents the splice donor (SD) and RNA packaging (Ψ) hairpins. In the LDI structure, an extended RNA packaging (ΨE) hairpin is folded, which includes the splice donor site and gag coding sequences. The gag initiation codon is engaged in a long distance base pairing interaction with sequences in the upstream U5 region in the BMH structure, thus forming the evolutionarily conserved U5-AUG duplex. Therefore, the LDI-BMH equilibrium may affect not only the process of RNA dimer formation but also translation initiation. In this study, we designed mutations in the 3′-terminal region of the leader RNA that alter the equilibrium of the LDI-BMH structures. The mutant leader RNAs are affected in RNA dimer formation, but not in their translation efficiency. These results indicate that the LDI-BMH status does not regulate HIV-1 RNA translation, despite the differential presentation of the gag initiation codon in both leader RNA structures. |
| Databáze: | OpenAIRE |
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