The importance of RNA modifications: From cells to muscle physiology

2021 ◽  
Author(s):  
Anindhya Sundar Das ◽  
Juan D. Alfonzo ◽  
Federica Accornero
Keyword(s):  
Muscle Physiology ◽  
Rna Modifications

Application and Evaluation of Case-Based Learning as a Part of Early Clinical Exposure for Undergraduate Medical Education Program

2020 ◽  
Vol 5 (08) ◽  
pp. 284-288
Author(s):  
Vandana Daulatabad ◽  
Prafull K. ◽  
Dr. Surekha S. Kadadi-Patil ◽  
Ramesh S. Patil
Keyword(s):  
Medical Education ◽  
Research Centre ◽  
Muscle Physiology ◽  
Case Scenario ◽  
Clinical Exposure ◽  
Clinical Scenarios ◽  
Case Based Learning ◽  
Nerve Muscle ◽  
Case Based ◽  
Early Clinical Exposure

Introduction: Medical Education is witnessing a significant transition and global shift towards competency based medical education (CBME) which includes early clinical exposure (ECE) program to help students apply and correlate principles of preclinical subjects with clinical scenarios, in various forms and in a variety of settings. One of the easy and feasible methods of ECE being Case Based Learning (CBL), our study aimed to design a case scenario and to evaluate impact of case base learning as a part of ECE module in first year undergraduate medical teaching program in nerve muscle physiology. Methods: The present study was conducted in 96 students at Ashwini Rural Medical College Hospital and Research Centre, Solapur after obtaining institutional ethics committee approval. 3 hrs session of CBL was conducted for a case scenario on myasthenia gravis in the nerve muscle physiology module. The students’ responses on pre-test, post-test and their insights regarding the CBL were taken through a pre validated questionnaire using 5-point Likert scale. Results: High impact of CBL was seen as significant improvement in student’s performance. Maximum students felt CBL to be easy method of learning and was highly appreciated through their feedback. Conclusion: CBL was found to have positive impact on understanding and perception of topic. CBL helped students to understand, evaluate, analyze, diagnose and interpret the case, paving them towards newer approach of self-directed and vertical integrated learning. CBL is easier, feasible an effective method among other early clinical exposure methods as it involves students in deeper and self-directed active learning, encouraging and promoting them to reach higher levels of cognitive domain of Bloom’s taxonomy. This method will be very useful in its practical implementation during online classes for ECE module in the threat of COVID 19 situation as well.

Store-Operated Ca2+ Entry in Muscle Physiology

2007 ◽  
Vol 1 (1) ◽  
pp. 87-95
Author(s):  
Marco Brotto ◽  
Noah Weisleder ◽  
Jianjie Ma
Keyword(s):  
Muscle Physiology

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 Magnesium Deficiency Alters Expression of Genes Critical for Muscle Magnesium Homeostasis and Physiology in Mice

Nutrients ◽  
2021 ◽  
Vol 13 (7) ◽  
pp. 2169
Author(s):  
Dominique Bayle ◽  
Cécile Coudy-Gandilhon ◽  
Marine Gueugneau ◽  
Sara Castiglioni ◽  
Monica Zocchi ◽  
...  
Keyword(s):  
Gastrocnemius Muscle ◽  
Magnesium Deficiency ◽  
Mitochondrial Dynamics ◽  
Body Weight Gain ◽  
Whole Body ◽  
Muscle Physiology ◽  
Deficient Diet ◽  
Muscle Weight ◽  
Magnesium Homeostasis ◽  
Expression Of Genes

Chronic Mg2+ deficiency is the underlying cause of a broad range of health dysfunctions. As 25% of body Mg2+ is located in the skeletal muscle, Mg2+ transport and homeostasis systems (MgTHs) in the muscle are critical for whole-body Mg2+ homeostasis. In the present study, we assessed whether Mg2+ deficiency alters muscle fiber characteristics and major pathways regulating muscle physiology. C57BL/6J mice received either a control, mildly, or severely Mg2+-deficient diet (0.1%; 0.01%; and 0.003% Mg2+ wt/wt, respectively) for 14 days. Mg2+ deficiency slightly decreased body weight gain and muscle Mg2+ concentrations but was not associated with detectable variations in gastrocnemius muscle weight, fiber morphometry, and capillarization. Nonetheless, muscles exhibited decreased expression of several MgTHs (MagT1, CNNM2, CNNM4, and TRPM6). Moreover, TaqMan low-density array (TLDA) analyses further revealed that, before the emergence of major muscle dysfunctions, even a mild Mg2+ deficiency was sufficient to alter the expression of genes critical for muscle physiology, including energy metabolism, muscle regeneration, proteostasis, mitochondrial dynamics, and excitation–contraction coupling.

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.

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