HIV-1 as RNA evolution machine

Berkhout, Ben

doi:10.4161/rna.8.2.14801

Cited by 13 publications

(11 citation statements)

References 66 publications

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“…Altering the site of polyadenylation can truncate protein open reading frames, change splicing patterns or alter mRNA posttranscriptional regulation by shortening the 3′ untranslated region (UTR) and removing sites for miRNA or RNA binding factor interactions [53]. Interestingly, HIV has two polyadenylation signals in its mRNA as a result of the duplicated signal present in the LTR regions [56]. The virus must suppress use of the upstream 5′ polyadenylation site or the short mRNA that is generated will not contain an open reading frame.…”

Section: Introductionmentioning

confidence: 99%

Putting an ‘End’ to HIV mRNAs: capping and polyadenylation as potential therapeutic targets

Wilusz

2013

AIDS Res Ther

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Like most cellular mRNAs, the 5′ end of HIV mRNAs is capped and the 3′ end matured by the process of polyadenylation. There are, however, several rather unique and interesting aspects of these post-transcriptional processes on HIV transcripts. Capping of the highly structured 5′ end of HIV mRNAs is influenced by the viral TAT protein and a population of HIV mRNAs contains a trimethyl-G cap reminiscent of U snRNAs involved in splicing. HIV polyadenylation involves active repression of a promoter-proximal polyadenylation signal, auxiliary upstream regulatory elements and moonlighting polyadenylation factors that have additional impacts on HIV biology outside of the constraints of classical mRNA 3’ end formation. This review describes these post-transcriptional novelties of HIV gene expression as well as their implications in viral biology and as possible targets for therapeutic intervention.

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Section: Introductionmentioning

confidence: 99%

Putting an ‘End’ to HIV mRNAs: capping and polyadenylation as potential therapeutic targets

Wilusz

2013

AIDS Res Ther

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“…All the HIV-1 genomic and subgenomic RNAs share approximately the first 300 nt of their 5′-UTR. This sequence contains several well-characterized and conserved functional RNA domains12 including the trans -activator response (TAR) element3, the polyadenylation [poly(A)] region4, the primer-binding site (PBS)5, the dimerisation initiation site (DIS)6, the major splicing donor (SD)7 and part of the packaging signal (psi)8 (Fig. 1).…”

mentioning

confidence: 99%

Efficient HIV-1 inhibition by a 16 nt-long RNA aptamer designed by combining in vitro selection and in silico optimisation strategies

Sánchez‐Luque

Stich

Manrubia

et al. 2014

Sci Rep

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The human immunodeficiency virus type-1 (HIV-1) genome contains multiple, highly conserved structural RNA domains that play key roles in essential viral processes. Interference with the function of these RNA domains either by disrupting their structures or by blocking their interaction with viral or cellular factors may seriously compromise HIV-1 viability. RNA aptamers are amongst the most promising synthetic molecules able to interact with structural domains of viral genomes. However, aptamer shortening up to their minimal active domain is usually necessary for scaling up production, what requires very time-consuming, trial-and-error approaches. Here we report on the in vitro selection of 64 nt-long specific aptamers against the complete 5′-untranslated region of HIV-1 genome, which inhibit more than 75% of HIV-1 production in a human cell line. The analysis of the selected sequences and structures allowed for the identification of a highly conserved 16 nt-long stem-loop motif containing a common 8 nt-long apical loop. Based on this result, an in silico designed 16 nt-long RNA aptamer, termed RNApt16, was synthesized, with sequence 5′-CCCCGGCAAGGAGGGG-3′. The HIV-1 inhibition efficiency of such an aptamer was close to 85%, thus constituting the shortest RNA molecule so far described that efficiently interferes with HIV-1 replication.

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“…Iglesias and Garmarnik 5 relay how the equilibrium between linear and pseudo-circular forms of the Dengue virus genome is important for optimal viral multiplication. Berkhout 6 describes how both local and long-range RNA-RNA interactions in the HIV-1 genome are important for replication and the amazing ability of this virus to rapidly adapt when such interactions are perturbed. Mechanistic aspects of the minus-strand transfer step during HIV-1 reverse transcription and the RNA and protein co-factors involved are reviewed by Piekna-Przybylska and Bambara 7 , while the fascinating replication of viroids and similar non-coding RNA replicons that involves rolling circle intermediates are described by Flores et al 8 .…”

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confidence: 99%