Translational Recoding and RNA Modifications

2005 ◽  
pp. 309-340 ◽  
Author(s):  
Olivier Namy ◽  
François Lecointe ◽  
Henri Grosjean ◽  
Jean-Pierre Rousset
Keyword(s):  
Rna Modifications

Current RNA-based Therapeutics in Clinical Trials

2019 ◽  
Vol 19 (3) ◽  
pp. 172-196 ◽  
Author(s):  
Ling-Yan Zhou ◽  
Zhou Qin ◽  
Yang-Hui Zhu ◽  
Zhi-Yao He ◽  
Ting Xu
Keyword(s):  
Clinical Trials ◽  
Rapid Development ◽  
Genetic Diseases ◽  
Three Dimensional ◽  
Therapeutic Effects ◽  
Messenger Rnas ◽  
Small Interfering Rnas ◽  
Rna Modifications ◽  
Guide Rna ◽  
Endogenous Genes

Long-term research on various types of RNAs has led to further understanding of diverse mechanisms, which eventually resulted in the rapid development of RNA-based therapeutics as powerful tools in clinical disease treatment. Some of the developing RNA drugs obey the antisense mechanisms including antisense oligonucleotides, small interfering RNAs, microRNAs, small activating RNAs, and ribozymes. These types of RNAs could be utilized to inhibit/activate gene expression or change splicing to provide functional proteins. In the meantime, some others based on different mechanisms like modified messenger RNAs could replace the dysfunctional endogenous genes to manage some genetic diseases, and aptamers with special three-dimensional structures could bind to specific targets in a high-affinity manner. In addition, the recent most popular CRISPR-Cas technology, consisting of a crucial single guide RNA, could edit DNA directly to generate therapeutic effects. The desired results from recent clinical trials indicated the great potential of RNA-based drugs in the treatment of various diseases, but further studies on improving delivery materials and RNA modifications are required for the novel RNA-based drugs to translate to the clinic. This review focused on the advances and clinical studies of current RNA-based therapeutics, analyzed their challenges and prospects.

scholarly journals Regulation of RNA stability at the 3′ end

2020 ◽  
Vol 0 (0) ◽  
Author(s):  
Mallory I. Frederick ◽  
Ilka U. Heinemann
Keyword(s):  
Mrna Decay ◽  
Rna Stability ◽  
Rna Modifications ◽  
Dual Roles ◽  
Cellular Pathways ◽  
Low Levels

AbstractRNA homeostasis is regulated by a multitude of cellular pathways. Although the addition of untemplated adenine residues to the 3′ end of mRNAs has long been known to affect RNA stability, newly developed techniques for 3′-end sequencing of RNAs have revealed various unexpected RNA modifications. Among these, uridylation is most recognized for its role in mRNA decay but is also a key regulator of numerous RNA species, including miRNAs and tRNAs, with dual roles in both stability and maturation of miRNAs. Additionally, low levels of untemplated guanidine and cytidine residues have been observed as parts of more complex tailing patterns.

scholarly journals PANDORA-seq expands the repertoire of regulatory small RNAs by overcoming RNA modifications

2021 ◽  
Author(s):  
Junchao Shi ◽  
Yunfang Zhang ◽  
Dongmei Tan ◽  
Xudong Zhang ◽  
Menghong Yan ◽  
...  
Keyword(s):  
Small Rnas ◽  
Rna Modifications

scholarly journals Histone lactylation drives oncogenesis by facilitating m6A reader protein YTHDF2 expression in ocular melanoma

2021 ◽  
Vol 22 (1) ◽  
Author(s):  
Jie Yu ◽  
Peiwei Chai ◽  
Minyue Xie ◽  
Shengfang Ge ◽  
Jing Ruan ◽  
...  
Keyword(s):  
Macrophage Polarization ◽  
Regulation Of Gene Expression ◽  
Metabolic Stress ◽  
Ocular Melanoma ◽  
Rna Modifications ◽  
M1 Macrophage ◽  
Melanoma Therapy

Abstract Background Histone lactylation, a metabolic stress-related histone modification, plays an important role in the regulation of gene expression during M1 macrophage polarization. However, the role of histone lactylation in tumorigenesis remains unclear. Results Here, we show histone lactylation is elevated in tumors and is associated with poor prognosis of ocular melanoma. Target correction of aberrant histone lactylation triggers therapeutic efficacy both in vitro and in vivo. Mechanistically, histone lactylation contributes to tumorigenesis by facilitating YTHDF2 expression. Moreover, YTHDF2 recognizes the m6A modified PER1 and TP53 mRNAs and promotes their degradation, which accelerates tumorigenesis of ocular melanoma. Conclusion We reveal the oncogenic role of histone lactylation, thereby providing novel therapeutic targets for ocular melanoma therapy. We also bridge histone modifications with RNA modifications, which provides novel understanding of epigenetic regulation in tumorigenesis.

scholarly journals MYC-targeted WDR4 promotes proliferation, metastasis, and sorafenib resistance by inducing CCNB1 translation in hepatocellular carcinoma

2021 ◽  
Vol 12 (7) ◽  
Author(s):  
Peng Xia ◽  
Hao Zhang ◽  
Kequan Xu ◽  
Xiang Jiang ◽  
Meng Gao ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
Epithelial Mesenchymal Transition ◽  
P53 Protein ◽  
Rna Modifications ◽  
M Cell ◽  
Mesenchymal Transition ◽  
Akt Phosphorylation ◽  
Repeat Domain ◽  
Cell Cycle Transition

AbstractHepatocellular carcinoma (HCC) is one of the most common malignancies worldwide. However, there still remains a lack of effective diagnostic and therapeutic targets for this disease. Increasing evidence demonstrates that RNA modifications play an important role in the progression of HCC, but the role of the N7-methylguanosine (m7G) methylation modification in HCC has not been properly evaluated. Thus, the goal of the present study was to investigate the function and mechanism of the m7G methyltransferase WD repeat domain 4 (WDR4) in HCC as well as its clinical relevance and potential value. We first verified the high expression of WDR4 in HCC and observed that upregulated WDR4 expression increased the m7G methylation level in HCC. WDR4 promoted HCC cell proliferation by inducing the G2/M cell cycle transition and inhibiting apoptosis in addition to enhancing metastasis and sorafenib resistance through epithelial-mesenchymal transition (EMT). Furthermore, we observed that c-MYC (MYC) can activate WDR4 transcription and that WDR4 promotes CCNB1 mRNA stability and translation to enhance HCC progression. Mechanistically, we determined that WDR4 enhances CCNB1 translation by promoting the binding of EIF2A to CCNB1 mRNA. Furthermore, CCNB1 was observed to promote PI3K and AKT phosphorylation in HCC and reduce P53 protein expression by promoting P53 ubiquitination. In summary, we elucidated the MYC/WDR4/CCNB1 signalling pathway and its impact on PI3K/AKT and P53. Furthermore, the result showed that the m7G methyltransferase WDR4 is a tumour promoter in the development and progression of HCC and may act as a candidate therapeutic target in HCC treatment.

Hypoxia-induced alteration of RNA modifications in the mouse testis and sperm

2021 ◽  
Author(s):  
Tong He ◽  
Huanping Guo ◽  
Xipeng Shen ◽  
Xiao Wu ◽  
Lin Xia ◽  
...  
Keyword(s):  
Hypobaric Hypoxia ◽  
Environmental Changes ◽  
Epigenetic Inheritance ◽  
Transcriptional Regulators ◽  
Extreme Environment ◽  
Mouse Testis ◽  
Rna Modification ◽  
Rna Modifications ◽  
Sperm Counts ◽  
Health Studies

Abstract Hypobaric hypoxia as an extreme environment in a plateau may have deleterious effects on human health. Studies have indicated that rush entry into a plateau may reduce male fertility and manifest in decreased sperm counts and weakened sperm motility. RNA modifications are sensitive to environmental changes and have recently emerged as novel post-transcriptional regulators in male spermatogenesis and intergenerational epigenetic inheritance. In the present study, we generated a mouse hypoxia model simulating the environment of 5500 meters in altitude for 35 days, which led to compromised spermatogenesis, decreased sperm counts, and an increased sperm deformation rate. Using this hypoxia model, we further applied our recently developed high-throughput RNA modification quantification platform based on LC–MS/MS, which exhibited the capacity to simultaneously examine 25 types of RNA modifications. Our results revealed an altered sperm RNA modifications signature in the testis (6 types) and mature sperm (11 types) under the hypoxia model, with 4 types showing overlap (Am, Gm, m7G, and m22G). Our data first drew the signature of RNA modification profiles and comprehensively analyzed the alteration of RNA modification levels in mouse testis and sperm under a mouse hypoxia model. These data may be highly related to human conditions under a similar hypoxia environment.

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