A G‐quadruplex‐forming RNA aptamer binds to the MTG8 TAFH domain and dissociates the leukemic AML1‐MTG8 fusion protein from DNA

Fukunaga, Jun-ichi; Nomura, Yusuke; Tanaka, Yoichiro; Torigoe, Hidetaka; Nakamura, Yoshikazu; Sakamoto, Taiichi; Kozu, Tomoko

doi:10.1002/1873-3468.13914

Cited by 4 publications

(2 citation statements)

References 70 publications

(80 reference statements)

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“…The imino proton resonances between 10.5 and 12.5 ppm are characteristic for G-quadruplex formation [30], consistent with that iMyo01 having no cytosine and therefore no G:C base pair. Since the G-quadruplex structure is stabilized by K + [31], it is considered that the KCl-induced shift of the imino proton spectrum of iMyo01 represents the stabilization of its G-quadruplex by K + binding.…”

Section: Imyo01 Forms a G-quadruplex Structuresupporting

confidence: 76%

Development of the 12-Base Short Dimeric Myogenetic Oli-godeoxynucleotide That Induces Myogenic Differentiation

Umezawa,

Ikeda,

Sakamoto

et al. 2024

Preprint

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A myogenetic oligodeoxynucleotide (myoDN), iSN04 (5'-AGA TTA GGG TGA GGG TGA-3'), is a single-stranded 18-base telomeric DNA that serves as an anti-nucleolin aptamer and induces myogenic differentiation, which is expected to be a nucleic acid drug for the prevention of disease-associated muscle wasting. To improve the drug efficacy and synthesis cost of myoDN, shortening the sequence while maintaining its structure-based function is a major challenge. Here, we report the novel 12-base non-telomeric myoDN, iMyo01 (5'-TTG GGT GGG GAA-3'), which has comparable myogenic activity to iSN04. iMyo01 as well as iSN04 promoted myotube formation of primary-cultured human myoblasts with upregulation of myogenic gene expression. Both iMyo01 and iSN04 interacted with nucleolin, but iMyo01 did not bind to berberine, the isoquinoline alkaloid that stabilizes iSN04. Nuclear magnetic resonance revealed that iMyo01 forms a G-quadruplex structure despite its short sequence. Native polyacrylamide gel electrophoresis and computational molecular dynamics simulation indicated that iMyo01 forms a homodimer to generate a G-quadruplex. These results provide new insights into the aptamer truncation technology that preserves aptamer conformation and bioactivity for the development of efficient nucleic acid drugs.

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Section: Imyo01 Forms a G-quadruplex Structuresupporting

confidence: 76%

Development of the 12-Base Short Dimeric Myogenetic Oli-godeoxynucleotide That Induces Myogenic Differentiation

Umezawa,

Ikeda,

Sakamoto

et al. 2024

Preprint

Self Cite

View full text Add to dashboard Cite

show abstract

“…After titration with 50 mM KCl, the NMR spectrum changed significantly, but seven sharp (arrows) and four broad (arrowheads) signals were observed, similar to those in the absence of KCl. The imino proton resonances between 10.5 and 12.5 ppm are characteristic for G-quadruplex formation [ 30 ], consistent with iMyo01 having no cytosine and therefore no G:C base pair. Since the G-quadruplex structure is stabilized by K + [ 31 ], it is considered that the KCl-induced shift of the imino proton spectrum of iMyo01-DNA represents the stabilization of its G-quadruplex by K + binding.…”

Section: Resultsmentioning

confidence: 75%

Development of the 12-Base Short Dimeric Myogenetic Oligodeoxynucleotide That Induces Myogenic Differentiation

Umezawa,

Ikeda,

Sakamoto

et al. 2024

BioTech

Self Cite

View full text Add to dashboard Cite

A myogenetic oligodeoxynucleotide (myoDN), iSN04 (5′-AGA TTA GGG TGA GGG TGA-3′), is a single-stranded 18-base telomeric DNA that serves as an anti-nucleolin aptamer and induces myogenic differentiation, which is expected to be a nucleic acid drug for the prevention of disease-associated muscle wasting. To improve the drug efficacy and synthesis cost of myoDN, shortening the sequence while maintaining its structure-based function is a major challenge. Here, we report the novel 12-base non-telomeric myoDN, iMyo01 (5′-TTG GGT GGG GAA-3′), which has comparable myogenic activity to iSN04. iMyo01 as well as iSN04 promoted myotube formation of primary-cultured human myoblasts with upregulation of myogenic gene expression. Both iMyo01 and iSN04 interacted with nucleolin, but iMyo01 did not bind to berberine, the isoquinoline alkaloid that stabilizes iSN04. Nuclear magnetic resonance revealed that iMyo01 forms a G-quadruplex structure despite its short sequence. Native polyacrylamide gel electrophoresis and a computational molecular dynamics simulation indicated that iMyo01 forms a homodimer to generate a G-quadruplex. These results provide new insights into the aptamer truncation technology that preserves aptamer conformation and bioactivity for the development of efficient nucleic acid drugs.

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Structure and Folding Patterns of RNA G-Quadruplexes

Uttamrao,

Sundaresan,

Rathinavelan

2023

RNA Technologies

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A G‐quadruplex‐forming RNA aptamer binds to the MTG8 TAFH domain and dissociates the leukemic AML1‐MTG8 fusion protein from DNA

Cited by 4 publications

References 70 publications

Development of the 12-Base Short Dimeric Myogenetic Oli-godeoxynucleotide That Induces Myogenic Differentiation

Development of the 12-Base Short Dimeric Myogenetic Oli-godeoxynucleotide That Induces Myogenic Differentiation

Development of the 12-Base Short Dimeric Myogenetic Oligodeoxynucleotide That Induces Myogenic Differentiation

Structure and Folding Patterns of RNA G-Quadruplexes

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