High-Throughput Profiling of Peptide–RNA Interactions Using Peptide Microarrays

Pai, Jaeyoung; Yoon, Tae‐Jin; Kim, Nam Doo; Lee, Im Soon; Yu, Jaehoon; Shin, Injae

doi:10.1021/ja309760g

Cited by 41 publications

(49 citation statements)

References 57 publications

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“…The peptides used in this study were synthesized on a solid support employing a conventional Fmoc/t-Bu strategy (Supplementary Table S8)36. Binding of the Mad1 and SAP25 peptides to mouse Sin3A PAH1 (residues 114–195) and PAH2 (residues 295–385) was determined using fluorescence polarization.…”

Section: Resultsmentioning

confidence: 99%

Suppression of Sin3A activity promotes differentiation of pluripotent cells into functional neurons

Halder

Lee

Hyun

et al. 2017

Sci Rep

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Sin3 is a transcriptional corepressor for REST silencing machinery that represses multiple neuronal genes in non-neuronal cells. However, functions of Sin3 (Sin3A and Sin3B) in suppression of neuronal phenotypes are not well characterized. Herein we show that Sin3A knockdown impedes the repressive activity of REST and enhances differentiation of pluripotent P19 cells into electrophysiologically active neurons without inducing astrogenesis. It is also found that silencing Sin3B induces neurogenesis of P19 cells with a lower efficiency than Sin3A knockdown. The results suggest that Sin3A has a more profound effect on REST repressive machinery for silencing neuronal genes in P19 cells than Sin3B. Furthermore, we show that a peptide inhibitor of Sin3A-REST interactions promotes differentiation of P19 cells into functional neurons. Observations made in studies using genetic deletion and a synthetic inhibitor suggests that Sin3A plays an important role in the repression of neuronal genes by the REST regulatory mechanism.

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Section: Resultsmentioning

confidence: 99%

Suppression of Sin3A activity promotes differentiation of pluripotent cells into functional neurons

Halder

Lee

Hyun

et al. 2017

Sci Rep

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“…5 It has been implicated that the internal residues of the peptide 1 is associate with RNA binding. 5 We deleted three amino acids at the C-terminus of peptide 1 and made a truncated construct of peptide 1' (LKKLLKLLKKLLK) to characterize the tertiary interaction between the peptide 1' and HCV IRES domain IV. In the protein-free form of HCV IRES, the domain IV forms a small hairpin where the start codon AUG is located at the apical loop ( Figure 1A).…”

Section: Resultsmentioning

confidence: 99%

“…4 Previously, an L-and K-rich peptide that strongly binds to the HCV IRES domain IV hairpin was reported. 5 Here, we report further structural characterization of the tertiary interaction between the peptide and HCV IRES domain IV RNA using NMR methods. The chemical shift perturbation (CSP) studies indicate that the peptide preferably binds to the upper stem of the IRES RNA, suggesting that this peptide would inhibit the denaturation of the domain IV hairpin structure.…”

Section: Introductionmentioning

confidence: 95%

Structural Studies of Peptide Binding Interaction of HCV IRES Domain IV

Shin¹,

Bang²,

Song³

et al. 2017

Journal of the Korean Magnetic Resonance Society

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The hepatitis C virus (HCV) internal ribosome entry site (IRES) is an RNA structure located in the 5'-UTR of the HCV RNA genome. The HCV IRES consists of four domains I, II, III, and IV, where domains II -IV are recognized by 40S ribosomal subunit and the domain III is bound to eukaryotic initiation factor 3 (eIF3) for translation initiation. Here, we have characterized the tertiary interaction between an L-/K-rich peptide and the HCV IRES domain IV. To probe the peptide binding interface in RNA, we synthesized 13 C-and 15 Ndouble labeled RNA and the binding site was identified by using the chemical shift perturbation (CSP) NMR methods. Our results showed that the peptide binds to the upper stem of the IRES domain IV, indicating that the tertiary interaction between the IRES domain IV and the peptide would disrupt the initiation of translation of HCV mRNA by blocking the start codon exposure. This study will provide an insight into the new peptide-based anti-viral drug design targeting HCV IRES RNA.

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“…23,24 Furthermore, previous studies have shown that amphiphilic α-helical peptides can selectively and strongly bind to hairpin RNAs. 25,26,27 In accordance with this idea, we hypothesized the existence of peptide(s) that can affect miR29 expression by up-regulating p53 activity in cancer cells.…”

Section: Introductionmentioning

confidence: 86%

An Amphiphilic Peptide Induces Apoptosis Through the miR29b-p53 Pathway in Cancer Cells

Kim

Lee

Kang

et al. 2016

Molecular Therapy - Nucleic Acids

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Peptides have been in the limelight, as therapeutic agents for cancer treatment through various applications due to their high target selectivity and exceptional ability to penetrate the cell membrane. Recent studies have revealed that synthesized peptides bind to hairpin structures of RNA that affect their activities such as changing the efficacy of microRNA maturation. MicroRNA-mediated p53 activation by the microRNA-29 (miR29) family is one of the most important regulatory pathways in cancer therapeutics. By targeting the suppressors of p53, a tumor suppressor protein, miR29 induces apoptosis of cancer cells through p53 stabilization. Here, we identify a novel synthesized amphiphilic peptide, LK-L1C/K6W/L8C, which enhances expression of miR29b and promotes p53 activity. In the presence of LK-L1C/K6W/L8C, pre-miR29b preferentially forms a complex with the Dicer protein through interaction of LK-L1C/K6W/L8C with the terminal loop region of pre-miR29b, leading to an increase in Dicer processing. Furthermore, LK-L1C/K6W/L8C stimulates apoptosis by improving p53 stability in miR29-inducible HeLa and MCF7 cells. Collectively, our study shows that a peptide can directly influence the miR29b-mediated p53 activation pathway in cancer cells. Therefore, our findings provide the basis for a new, potentially promising peptide-based drug for cancer therapy.

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High-Throughput Profiling of Peptide–RNA Interactions Using Peptide Microarrays

Cited by 41 publications

References 57 publications

Suppression of Sin3A activity promotes differentiation of pluripotent cells into functional neurons

Suppression of Sin3A activity promotes differentiation of pluripotent cells into functional neurons

Structural Studies of Peptide Binding Interaction of HCV IRES Domain IV

An Amphiphilic Peptide Induces Apoptosis Through the miR29b-p53 Pathway in Cancer Cells

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