The effect of cell penetrating peptide-conjugated coactivator-associated arginine methyltransferase 1 (CPP-CARM1) on the cloned mouse embryonic development

Bang, Jin-Young; Lee, Eun‐Hye; Lee, Ah Reum; Lee, Jin I.; Choi, Seo Hye; Seol, Dong-Won; Park, Chang-Hwan; Lee, Dong Ryul

doi:10.1038/s41598-018-35077-0

Cited by 6 publications

(3 citation statements)

References 30 publications

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“…Next, we investigated whether P8 could hinder the UPF1-LIN28A interaction by competing with endogenous UPF1 for LIN28A. To deliver the peptides into cells, we first generated four N-terminal CPP (N-KKKWCRKKK-C)-conjugated peptides 40 (Fig. 5a ).…”

Section: Resultsmentioning

confidence: 99%

Role of UPF1-LIN28A interaction during early differentiation of pluripotent stem cells

Jung,

Ko,

Ahn

et al. 2024

Nat Commun

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UPF1 and LIN28A are RNA-binding proteins involved in post-transcriptional regulation and stem cell differentiation. Most studies on UPF1 and LIN28A have focused on the molecular mechanisms of differentiated cells and stem cell differentiation, respectively. We reveal that LIN28A directly interacts with UPF1 before UPF1-UPF2 complexing, thereby reducing UPF1 phosphorylation and inhibiting nonsense-mediated mRNA decay (NMD). We identify the interacting domains of UPF1 and LIN28A; moreover, we develop a peptide that impairs UPF1-LIN28A interaction and augments NMD efficiency. Transcriptome analysis of human pluripotent stem cells (hPSCs) confirms that the levels of NMD targets are significantly regulated by both UPF1 and LIN28A. Inhibiting the UPF1-LIN28A interaction using a CPP-conjugated peptide promotes spontaneous differentiation by repressing the pluripotency of hPSCs during proliferation. Furthermore, the UPF1-LIN28A interaction specifically regulates transcripts involved in ectodermal differentiation. Our study reveals that transcriptome regulation via the UPF1-LIN28A interaction in hPSCs determines cell fate.

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Section: Resultsmentioning

confidence: 99%

Role of UPF1-LIN28A interaction during early differentiation of pluripotent stem cells

Jung,

Ko,

Ahn

et al. 2024

Nat Commun

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“…Thus, we speculate that CARM1 may activate Hippo signaling to facilitate ICM lineage specification in pigs. On the other hand, CARM1 is required for differentiation of epithelial cells ( O’Brien et al, 2010 ) and enforced expression of CARM1 promoted CDX2 transcription and increased TE cell number in murine cloned blastocysts ( Bang et al, 2018 ). It is thus likely that CARM1 elevates the expression of trophectoderm genes to promote TE lineage specification.…”

Section: Discussionmentioning

confidence: 99%

Histone Arginine Methyltransferase CARM1-Mediated H3R26me2 Is Essential for Morula-to-Blastocyst Transition in Pigs

Cao

Yin³

et al. 2021

Front. Cell Dev. Biol.

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Coactivator-associated arginine methyltransferase 1 (CARM1) is involved in both establishment of first pluripotent lineage and pluripotency maintenance of embryonic stem cells (ESCs) in mice. However, the histone substrates and role of CARM1 in early embryonic development remain largely unknown. Here, we show that CARM1 specifically catalyzes H3R26me2 to promote porcine blastocyst formation. The putative histone substrates of CARM1, including H3R2me2, H3R17me2, and H3R26me2, are present in pig early embryos. The changes of CARM1 mRNA during early embryogenesis parallel that of H3R26me2. Functional studies using a combinational approach of chemical inhibition and RNA interference (RNAi) showed that catalytic activity inhibition of CARM1 protein or knockdown (KD) of CARM1 mRNA did not alter the levels of both H3R2me2 and H3R17me2, but significantly reduced H3R26me2 levels in porcine embryos. Furthermore, CARM1 inhibition or KD did not affect embryo development to the 2-cell, 4-cell, 8-cell, and morula stages, but severely compromised blastocyst development. CARM1 knocked down embryos that developed to the blastocyst stage had fewer total cells, inner cell mass (ICM), and trophectoderm (TE) cells. Mechanistically, single embryo RNA-sequencing analysis revealed that CARM1 KD altered the transcriptome characterized by downregulation of key genes associated with Hippo and PI3K-AKT signaling pathways. Taken together, these results demonstrate that CARM1 specifically catalyzes H3R26me2 in porcine embryos and participates in blastocyst development.

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“…CPPs that are arginine-and lysine-rich cationic peptides can readily enter cells not only by themselves but also by carrying other macromolecular cargos [32,33]. The KRK motif, which encompasses sequences such as CGKRK, Pep-1, and KRK, is frequently observed in a wide range of CPPs [34][35][36]. Notably, through the utilization of Random Forest-based prediction models, specific dipeptides (RR, KK, KR, RK) and tripeptides (RRR, KKK, KKR, KRK, RKK) have been identified as significant determinants contributing to the cell-penetrating properties of peptides, underscoring the importance of diverse sequential features [37].…”

Section: Introductionmentioning

confidence: 99%

Enhancing the activity of β-lactamase inhibitory protein-II with cell-penetrating peptide against KPC-2-carrying Klebsiella pneumoniae

Chatupheeraphat,

Peamchai,

Kaewsai

et al. 2024

PLoS ONE

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Carbapenem-resistant Enterobacterales (CRE) is considered a paramount threat due to its rapid spread and high mortality rate. Klebsiella pneumoniae carbapenemases (KPCs), specifically KPC-2, are prevalent enzymes responsible for carbapenem resistance in many countries. While combinations of antibiotics are commonly used, they must be tailored to match the remaining susceptibility of the infecting strains. Therefore, there is a need to develop the β-lactamase inhibitor to effectively address this issue. β-lactamase inhibitor protein (BLIP) and its variants, BLIP-I and BLIP-II, have demonstrated the ability to inhibit class A β-lactamases. In particular, BLIP-II shows strong binding to the KPC-2 carbapenemase, making it a potential candidate for inhibition. To improve the intracellular penetration of BLIP-II, a cell-penetrating peptide (CPP) was employed. In this study, a KRK-rich peptide was introduced at either the N-terminal or C-terminal region of tBLIP-II, excluding the signal sequence of the BLIP-II protein. tBLIP-II, tBLIP-II-CPP, and CPP-BLIP-II were successfully expressed, and the chimeric proteins retained inhibitory activity compared to tBLIP-II alone. It is apparent that homology modeling demonstrated neither the poly-histidine tag nor the CPP interfered with the essential interaction residues of tBLIP-II. Interestingly, BLIP-II-CPP exhibited the highest inhibitory activity, reducing the minimal inhibitory concentration (MIC) of meropenem by 8 folds. Moreover, the combination of tBLIP-CPP with meropenem significantly decreased the viable bacterial cell count compared to the combination of tBLIP-II with meropenem or meropenem alone. These findings suggest that tBLIP-CPP is a promising candidate for restoring carbapenem susceptibility against CRE and provides a valuable therapeutic option for infections caused by CRE.

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The effect of cell penetrating peptide-conjugated coactivator-associated arginine methyltransferase 1 (CPP-CARM1) on the cloned mouse embryonic development

Cited by 6 publications

References 30 publications

Role of UPF1-LIN28A interaction during early differentiation of pluripotent stem cells

Role of UPF1-LIN28A interaction during early differentiation of pluripotent stem cells

Histone Arginine Methyltransferase CARM1-Mediated H3R26me2 Is Essential for Morula-to-Blastocyst Transition in Pigs

Enhancing the activity of β-lactamase inhibitory protein-II with cell-penetrating peptide against KPC-2-carrying Klebsiella pneumoniae

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