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

Wilusz, Jeffrey

doi:10.1186/1742-6405-10-31

Cited by 20 publications

(19 citation statements)

References 77 publications

(89 reference statements)

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“…(Purcell and Martin 1993). • Polyadenylation signal, used to generate the 3′ end of the viral RNA (Wilusz 2013).…”

Section: Abbreviationsmentioning

confidence: 99%

Targeting the HIV RNA Genome: High-Hanging Fruit Only Needs a Longer Ladder

Grice

2015

Current Topics in Microbiology and Immunology

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Small molecules targeting the enzymes responsible for human immunodeficiency virus (HIV) maturation, DNA synthesis and its subsequent chromosomal integration as ribonucleotide-free double-stranded DNA remain the mainstay of combination antiretroviral therapy. For infected individuals harboring drug-susceptible virus, this approach has afforded complete or near-complete viral suppression. However, in the absence of a curative strategy, the predictable emergence of drug-resistant variants requires continued development of improved antiviral strategies, inherent to which is the necessity of identifying novel targets. Regulatory elementsRegulatory elements that mediate transcription, translation, nucleocytoplasmic transport, dimerization, packaging and reverse transcription of the (+) strand RNA genomeRNA genome should now be considered viable targets for small molecule, peptide- and oligonucleotide-based therapeuticsTherapeutics . Where target specificity and cellular penetration and toxicity have been the primary obstacle to successful "macromolecule therapeutics", this chapter summarizes (a) novel approaches targeting RNA motifs whose three-dimensional structure is critical for biological function and consequently may be less prone to resistance-conferring mutations and (b) improved methods for deliveryDelivery .

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“…(Purcell and Martin 1993). • Polyadenylation signal, used to generate the 3′ end of the viral RNA (Wilusz 2013).…”

Section: Abbreviationsmentioning

confidence: 99%

Targeting the HIV RNA Genome: High-Hanging Fruit Only Needs a Longer Ladder

Grice

2015

Current Topics in Microbiology and Immunology

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“…Not surprisingly, the 3΄ termini of many RNA viruses, including picornaviruses (2) and HIV (3), have also been found to possess poly(A) tails. Cellular mRNA receive poly(A) tails through the process of cleavage and polyadenylation where the pre-mRNA is co-transcriptionally cleaved and subsequently used as a substrate for poly(A) polymerase.…”

Section: Introductionmentioning

confidence: 99%

Poly(A)-ClickSeq: click-chemistry for next-generation 3΄-end sequencing without RNA enrichment or fragmentation

Routh

Jaworski

et al. 2017

Nucleic Acids Research

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The recent emergence of alternative polyadenylation (APA) as an engine driving transcriptomic diversity has stimulated the development of sequencing methodologies designed to assess genome-wide polyadenylation events. The goal of these approaches is to enrich, partition, capture and ultimately sequence poly(A) site junctions. However, these methods often require poly(A) enrichment, 3΄ linker ligation steps, and RNA fragmentation, which can necessitate higher levels of starting RNA, increase experimental error and potentially introduce bias. We recently reported a click-chemistry based method for generating RNAseq libraries called ‘ClickSeq’. Here, we adapt this method to direct the cDNA synthesis specifically toward the 3΄UTR/poly(A) tail junction of cellular RNA. With this novel approach, we demonstrate sensitive and specific enrichment for poly(A) site junctions without the need for complex sample preparation, fragmentation or purification. Poly(A)-ClickSeq (PAC-seq) is therefore a simple procedure that generates high-quality RNA-seq poly(A) libraries. As a proof-of-principle, we utilized PAC-seq to explore the poly(A) landscape of both human and Drosophila cells in culture and observed outstanding overlap with existing poly(A) databases and also identified previously unannotated poly(A) sites. Moreover, we utilize PAC-seq to quantify and analyze APA events regulated by CFIm25 illustrating how this technology can be harnessed to identify alternatively polyadenylated RNA.

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“…HIV provirus behaves like a cellular gene; it has its own promoter located in the 5' LTR and is rich in responsive elements for binding of several cellular transcription factors (Figure 4). It also has a 3' LTR, which ensures the viral mRNAs are polyadenylated and capped mimicking cellular transcripts [174] . Of note, both LTRs have the same sequence and the 3'LTR is transcribed into the 3' UTR of the viral transcripts.…”

Section: Virus: Hivmentioning

confidence: 99%

Post-transcriptional gene silencing, transcriptional gene silencing and human immunodeficiency virus

Méndez

2015

WJV

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

Cited by 20 publications

References 77 publications

Targeting the HIV RNA Genome: High-Hanging Fruit Only Needs a Longer Ladder

Targeting the HIV RNA Genome: High-Hanging Fruit Only Needs a Longer Ladder

Poly(A)-ClickSeq: click-chemistry for next-generation 3΄-end sequencing without RNA enrichment or fragmentation

Post-transcriptional gene silencing, transcriptional gene silencing and human immunodeficiency virus

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