Structural and thermodynamic signatures that define pseudotriloop RNA hairpins

Werf, Ramon van der; Wijmenga, Sybren S.; Heus, Hans A.; Olsthoorn, René C. L.

doi:10.1261/rna.039636.113

Cited by 8 publications

(7 citation statements)

References 30 publications

(59 reference statements)

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“…Upon Tat RBD binding, this apical loop is stabilized by the formation of a C 30 -G 34 base-pair, thus giving rise to the predicted pseudo-triloop configuration (Supplementary Fig. 10b ) 34 – 36 . G 26 though U 31 show NOEs representative of classical stacking interactions, after which there is a strand reversal with G 32 and G 33 oriented towards the minor groove face of the molecule.…”

Section: Resultsmentioning

confidence: 99%

HIV-1 Tat interactions with cellular 7SK and viral TAR RNAs identifies dual structural mimicry

Pham¹,

Salguero²,

Khan³

et al. 2018

Nat Commun

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The HIV Tat protein competes with the 7SK:HEXIM interaction to hijack pTEFb from 7SK snRNP and recruit it to the TAR motif on stalled viral transcripts. Here we solve structures of 7SK stemloop-1 and TAR in complex with Tat’s RNA binding domain (RBD) to gain insights into this process. We find that 7SK is peppered with arginine sandwich motifs (ASM)—three classical and one with a pseudo configuration. Despite having similar RBDs, the presence of an additional arginine, R52, confers Tat the ability to remodel the pseudo configuration, required for HEXIM binding, into a classical sandwich, thus displacing HEXIM. Tat also uses R52 to remodel the TAR bulge into an ASM whose structure is identical to that of the remodeled ASM in 7SK. Together, our structures reveal a dual structural mimicry wherein viral Tat and TAR have co-opted structural motifs present in cellular HEXIM and 7SK for productive transcription of its genome.

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Section: Resultsmentioning

confidence: 99%

HIV-1 Tat interactions with cellular 7SK and viral TAR RNAs identifies dual structural mimicry

Pham¹,

Salguero²,

Khan³

et al. 2018

Nat Commun

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“…Temperature‐ramping experiments were carried out from 10 to 90 °C at a rate of 1 °C min −1 using a Cary 300 Bio UV‐VIS spectrometer (Varian) equipped with a temperature controller. The T m was calculated from the first derivative of the melting curve …”

Section: Methodsmentioning

confidence: 99%

DNA‐Responsive Polyisocyanopeptide Hydrogels with Stress‐Stiffening Capacity

Deshpande¹,

Hammink²,

Das

et al. 2016

Adv Funct Materials

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Biological materials have evolved to combine a number of functionally relevant properties. They are sensitive to chemical and mechanical signals and respond to these signals in a highly specific manner. Many biological hydrogels possess the ability to stress-stiffen, a property that is difficult to mimic in synthetic systems. A novel synthetic hydrogel is described that possesses stress-stiffening behavior in the biologically relevant stress regime and, at the same time, contains DNA cross-links as stimuli-responsive elements. The hydrogel scaffold is composed of oligo(ethylene glycol)-functionalized polyisocyanopeptides (PIC), which show a sol-to-gel transition upon increasing the temperature. It is shown that the mechanical properties of the hybrid hydrogel depend on DNA cross-linker concentration and temperature. At high temperature, a hydrophobically bundled stress-stiffening PIC network forms. By contrast, gel formation is controlled by DNA cross-linking at temperatures below the PIC sol-to-gel transition. The DNA cross-linked hydrogel also exhibits stress-stiffening behavior and its properties are controlled by the DNA cross-linker concentration. The hydrogel properties can further be tuned when using DNA cross-linkers with different melting temperature or when breaking cross-links by strand displacement. This clearly shows the potential of DNA cross-links as stimuli-responsive elements, highlighting the possible applications of this hybrid hydrogel as a new sensor

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“…Melting temperatures ( T m) were calculated from two heating and cooling runs according to van der Werf et al. ( 16 ).…”

Section: Methodsmentioning

confidence: 99%

G-quadruplexes within prion mRNA: the missing link in prion disease?

Olsthoorn

2014

Nucleic Acids Res

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Cellular ribonucleic acid (RNA) plays a crucial role in the initial conversion of cellular prion protein PrPC to infectious PrPSc or scrapie. The nature of this RNA remains elusive. Previously, RNA aptamers against PrPC have been isolated and found to form G-quadruplexes (G4s). PrPC binding to G4 RNAs destabilizes its structure and is thought to trigger its conversion to PrPSc. Here it is shown that PrP messenger RNA (mRNA) itself contains several G4 motifs, located in the octarepeat region. Investigation of the RNA structure in one of these repeats by circular dichroism, nuclear magnetic resonance and ultraviolet melting studies shows evidence of G4 formation. In vitro translation of full-length PrP mRNA, naturally harboring five consecutive G4 motifs, was specifically affected by G4-binding ligands, lending support to G4 formation in PrP mRNA. A possible role of PrP binding to its own mRNA and the role of anti-prion drugs, many of which are G4-binding ligands, in prion disease are discussed.

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Structural and thermodynamic signatures that define pseudotriloop RNA hairpins

Cited by 8 publications

References 30 publications

HIV-1 Tat interactions with cellular 7SK and viral TAR RNAs identifies dual structural mimicry

HIV-1 Tat interactions with cellular 7SK and viral TAR RNAs identifies dual structural mimicry

DNA‐Responsive Polyisocyanopeptide Hydrogels with Stress‐Stiffening Capacity

G-quadruplexes within prion mRNA: the missing link in prion disease?

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