Mini-peptide RPL41 attenuated retinal neovascularization by inducing degradation of ATF4 in oxygen-induced retinopathy mice

Geng, Wen; Feng, Qicheng; Ren, Jiaxu; Xiao, Sheng; Wang, Aiyuan

doi:10.1016/j.yexcr.2018.05.027

Cited by 17 publications

(9 citation statements)

References 37 publications

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“…It has also been proposed that some RPs, which exert extraribosomal functions, are driven by additional specific regulatory mechanisms [68,69]. This could be the case for RPL41 which was shown to be involved in a variety of processes such as degradation of transcription factor ATF4 and mitosis through its association with several cytoskeleton components [70,71].…”

Section: Discussionmentioning

confidence: 99%

Divergent effects of translation termination factor eRF3A and nonsense-mediated mRNA decay factor UPF1 on the expression of uORF carrying mRNAs and ribosome protein genes

Aliouat¹,

Hatin

Bertin

et al. 2019

RNA Biology

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2020) Divergent effects of translation termination factor eRF3A and nonsense-mediated mRNA decay factor UPF1 on the expression of uORF carrying mRNAs and ribosome protein genes, RNA Biology, 17:2, 227-239, ABSTRACTIn addition to its role in translation termination, eRF3A has been implicated in the nonsense-mediated mRNA decay (NMD) pathway through its interaction with UPF1. NMD is a RNA quality control mechanism, which detects and degrades aberrant mRNAs as well as some normal transcripts including those that harbour upstream open reading frames in their 5ʹ leader sequence. In this study, we used RNAsequencing and ribosome profiling to perform a genome wide analysis of the effect of either eRF3A or UPF1 depletion in human cells. Our bioinformatics analyses allow to delineate the features of the transcripts controlled by eRF3A and UPF1 and to compare the effect of each of these factors on gene expression. We find that eRF3A and UPF1 have very different impacts on the human transcriptome, less than 250 transcripts being targeted by both factors. We show that eRF3A depletion globally derepresses the expression of mRNAs containing translated uORFs while UPF1 knockdown derepresses only the mRNAs harbouring uORFs with an AUG codon in an optimal context for translation initiation. Finally, we also find that eRF3A and UPF1 have opposite effects on ribosome protein gene expression. Together, our results provide important elements for understanding the impact of translation termination and NMD on the human transcriptome and reveal novel determinants of ribosome biogenesis regulation. ARTICLE HISTORY

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Section: Discussionmentioning

confidence: 99%

Divergent effects of translation termination factor eRF3A and nonsense-mediated mRNA decay factor UPF1 on the expression of uORF carrying mRNAs and ribosome protein genes

Aliouat¹,

Hatin

Bertin

et al. 2019

RNA Biology

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“…Gene therapy and various gene delivery systems have been introduced; however, these strategies are accompanied by potential risks, largely due to their clinical transformation, such as infection, immunogenic response, or low expression efficiency (Blanquer, Grijpma, & Poot, 2015). As observed in previous studies, synthesized peptides can be used to target the precise protein domain and perform local injection, which greatly enhances the accuracy and efficiency of clinical application (Geng, Qin, Ren, Xiao, & Wang, 2018;Li et al, 2018). In the present study, the synthesized RPL41 peptide was used, which is analogous to the product of the tumor suppressor gene, Rpl41, and its exogenous application inhibited retinoblastoma cell growth.…”

Section: Discussionmentioning

confidence: 99%

“…In the future studies, we would perform further experiments on the more aggressive retinoblastoma cell lines such as RB355 and NCC‐Rb51 cell lines. Moreover, we administrated the RPL41 peptide by intravitreal injection in our previous study and found that the intravitreal injection of RPL41 peptide could efficiently suppress neovascularization in mice retina (Geng et al, 2018). Besides, intravitreal administration of chemotherapeutic agents has been recommended to be effective (Shields, Manjandavida, Arepalli et al, 2014).…”

Section: Discussionmentioning

confidence: 99%

RPL41 sensitizes retinoblastoma cells to chemotherapeutic drugs via ATF4 degradation

Geng

Ren

Shi

et al. 2020

Journal Cellular Physiology

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Retinoblastoma is the most common intraocular cancer with metastatic potential affecting infants and children. Although chemotherapy is available for retinoblastoma, side effects and drug resistance are frequent. Rpl41, encoding ribosomal protein L41 (RPL41), has been identified as a tumor suppressor gene, and its targeted degradation of activating transcription factor 4 (ATF4) produces an antitumor effect. The goal of the present study is to provide experimental evidence for the clinical application of a small peptide regimen in combination with chemotherapy for the treatment of retinoblastoma and to investigate the mechanism of their combined cytotoxicity. It was observed that treatment with the RPL41 peptide alone decreased the viability, migration, and invasion of retinoblastoma Y79 and Weri-Rb1 cells, in addition to promoting cell apoptosis and cell cycle arrest. Furthermore, RPL41 protein levels showed a significantly decreased trend in retinoblastoma specimens, whereas ATF4 protein levels tended to be increased. Mechanistically, ATF4 degradation as a result of RPL41 peptide treatment was observed in retinoblastoma Y79 and Weri-Rb1 cells. Most important, low-dose administration of the RPL41 peptide significantly enhanced the antitumor effect of carboplatin, and further analysis confirmed their synergistic effect as anti-retinoblastoma therapy, indicating that RPL41 sensitized Y79 and Weri-Rb1 retinoblastoma cells to carboplatin. Thus, our data provide a preclinical rationale for the exploration of the RPL41 peptide as a potential adjuvant to carboplatin treatment in retinoblastoma.

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“…The retinas were incubated in isolectin B4-594 (Invitrogen, Carlsbad, CA, United States) in a shaker at 4 °C overnight. Next, the glass slide was covered with an anti-radiation agent, and this agent was also applied to the retina[ 18 ]. The retinas were observed under a microscope (Eclipse NI, Nikon, Tokyo, Japan) and images were collected.…”

Section: Methodsmentioning

confidence: 99%

Expression and role of P-element-induced wimpy testis-interacting RNA in diabetic-retinopathy in mice

Yu¹,

Ren²,

Chen³

2021

WJD

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BACKGROUND As one of the major microvascular complications of diabetes, diabetic retinopathy (DR) is the leading cause of blindness in the working age population. Because the extremely complex pathogenesis of DR has not been fully clarified, the occurrence and development of DR is closely related to tissue ischemia and hypoxia and neovascularization The formation of retinal neovascularization (RNV) has great harm to the visual acuity of patients. AIM To investigate the expression of P-element-induced wimpy testis-interacting RNA (piRNA) in proliferative DR mice and select piRNA related to RNV. METHODS One hundred healthy C57BL/6J mice were randomly divided into a normal group as control group (CG) and proliferative DR (PDR) group as experimental group (EG), with 50 mice in each group. Samples were collected from both groups at the same time, and the lesions of mice were evaluated by hematoxylin and eosin staining and retinal blood vessel staining. The retinal tissues were collected for second-generation high-throughput sequencing, and the differentially expressed piRNA between the CG and EG was detected, and polymerase chain reaction (PCR) was conducted for verification. The differentially obtained piRNA target genes and expression profiles were enrichment analysis based on gene annotation (Gene Ontology) and Kyoto Encyclopedia of Genes and Genomes. RESULTS In the CG there was no perfusion area, neovascularization and endothelial nucleus broke through the inner boundary membrane of retinap. In the EG, there were a lot of nonperfused areas, new blood vessels and endothelial nuclei breaking through the inner boundary membrane of the retina. There was a statistically significant difference in the number of vascular endothelial nuclei breaking through the inner retinal membrane between the two groups. High-throughput sequencing analysis showed that compared with the CG, a total of 79 piRNAs were differentially expressed in EG, among which 43 piRNAs were up-regulated and 36 piRNAs were down-regulated. Bioinformatics analysis showed that the differentially expressed piRNAs were mainly concentrated in the signaling pathways of angiogenesis and cell proliferation. Ten piRNAs were selected for PCR, and the results showed that the expression of piR-MMU-40373735, piR-MMU-61121420, piR-MMU-55687822, piR-MMU-1373887 were high, and the expression of piR-MMU-7401535, piR-MMU-4773779, piR-MMU-1304999, and piR-MMU-5160126 were low, which were consistent with the sequencing results. CONCLUSION In the EG, the abnormal expression of piRNA is involved in the pathway of angiogenesis and cell proliferation, suggesting that piRNAs have some regulatory function in proliferative diabetic-retinopathy.

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Mini-peptide RPL41 attenuated retinal neovascularization by inducing degradation of ATF4 in oxygen-induced retinopathy mice

Cited by 17 publications

References 37 publications

Divergent effects of translation termination factor eRF3A and nonsense-mediated mRNA decay factor UPF1 on the expression of uORF carrying mRNAs and ribosome protein genes

Divergent effects of translation termination factor eRF3A and nonsense-mediated mRNA decay factor UPF1 on the expression of uORF carrying mRNAs and ribosome protein genes

RPL41 sensitizes retinoblastoma cells to chemotherapeutic drugs via ATF4 degradation

Expression and role of P-element-induced wimpy testis-interacting RNA in diabetic-retinopathy in mice

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