Novel Biochemical Tools for Probing HIV RNA Structure

Rausch, Jason W.; Sztuba-Solińska, Joanna; Lusvarghi, Sabrina; Grice, Stuart F. J. Le

doi:10.1007/978-1-4939-3046-3_7

Cited by 2 publications

(1 citation statement)

References 26 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…A normalized reactivity of 1.0 was defined as the average intensity of the top 10% most reactive peaks, where the most reactive 2% of all intensities were removed from the pool. The intensities of the next 8% most reactive peaks are averaged and all reactivities are divided by this average value, as previously described (36,37).…”

Section: Methodsmentioning

confidence: 99%

miR-122 and Ago interactions with the HCV genome alter the structure of the viral 5′ terminus

Chahal

Gebert

Gan

et al. 2019

Nucleic Acids Research

View full text Add to dashboard Cite

Hepatitis C virus (HCV) is a positive-sense RNA virus that interacts with the liver-specific microRNA, miR-122. miR-122 binds to two sites in the 5′ untranslated region (UTR) and this interaction promotes HCV RNA accumulation, although the precise role of miR-122 in the HCV life cycle remains unclear. Using biophysical analyses and Selective 2′ Hydroxyl Acylation analyzed by Primer Extension (SHAPE) we investigated miR-122 interactions with the 5′ UTR. Our data suggests that miR-122 binding results in alteration of nucleotides 1–117 to suppress an alternative secondary structure and promote functional internal ribosomal entry site (IRES) formation. Furthermore, we demonstrate that two hAgo2:miR-122 complexes are able to bind to the HCV 5′ terminus simultaneously and SHAPE analyses revealed further alterations to the structure of the 5′ UTR to accommodate these complexes. Finally, we present a computational model of the hAgo2:miR-122:HCV RNA complex at the 5′ terminus of the viral genome as well as hAgo2:miR-122 interactions with the IRES–40S complex that suggest hAgo2 is likely to form additional interactions with SLII which may further stabilize the HCV IRES. Taken together, our results support a model whereby hAgo2:miR-122 complexes alter the structure of the viral 5′ terminus and promote formation of the HCV IRES.

show abstract

Section: Methodsmentioning

confidence: 99%

miR-122 and Ago interactions with the HCV genome alter the structure of the viral 5′ terminus

Chahal

Gebert

Gan

et al. 2019

Nucleic Acids Research

View full text Add to dashboard Cite

show abstract

Designing metallodrugs with nuclease and protease activity

et al. 2016

View full text Add to dashboard Cite

The accidental discovery of cisplatin some 50 years ago generated renewed interest in metallopharmaceuticals. Beyond cisplatin, many useful metallodrugs have been synthesized for the diagnosis and treatment of various diseases, but toxicity concerns, and the propensity to induce chemoresistance and secondary cancers make it imperative to search for novel metallodrugs that address these limitations. The Amino Terminal Cu(ii) and Ni(ii) (ATCUN) binding motif has emerged as a suitable template to design catalytic metallodrugs with nuclease and protease activities. Unlike their classical counterparts, ATCUN-based metallodrugs exhibit low toxicity, employ novel mechanisms to irreversibly inactivate disease-associated genes or proteins providing in principle, a channel to circumvent the rapid emergence of chemoresistance. The ATCUN motif thus presents novel strategies for the treatment of many diseases including cancers, HIV and infections caused by drug-resistant bacteria at the genetic level. This review discusses their design, mechanisms of action and potential for further development to expand their scope of application.

show abstract

Novel Biochemical Tools for Probing HIV RNA Structure

Cited by 2 publications

References 26 publications

miR-122 and Ago interactions with the HCV genome alter the structure of the viral 5′ terminus

miR-122 and Ago interactions with the HCV genome alter the structure of the viral 5′ terminus

Designing metallodrugs with nuclease and protease activity

Contact Info

Product

Resources

About