scholarly journals Recent advances in dynamic m 6 A RNA modification

Open Biology ◽  
2016 ◽  
Vol 6 (4) ◽  
pp. 160003 ◽  
Author(s):  
Guangchao Cao ◽  
Hua-Bing Li ◽  
Zhinan Yin ◽  
Richard A. Flavell
Keyword(s):  
Rna Splicing ◽  
High Throughput Sequencing ◽  
Epigenetic Modification ◽  
Rna Modification ◽  
Sequencing Analysis ◽  
Biological Functions ◽  
Dynamic Regulation ◽  
The Past ◽  
Recent Advances

The identification of m 6 A demethylases and high-throughput sequencing analysis of methylated transcriptome corroborated m 6 A RNA epigenetic modification as a dynamic regulation process, and reignited its investigation in the past few years. Many basic concepts of cytogenetics have been revolutionized by the growing understanding of the fundamental role of m 6 A in RNA splicing, degradation and translation. In this review, we summarize typical features of methylated transcriptome in mammals, and highlight the ‘writers’, ‘erasers’ and ‘readers’ of m 6 A RNA modification. Moreover, we emphasize recent advances of biological functions of m 6 A and conceive the possible roles of m 6 A in the regulation of immune response and related diseases.

scholarly journals Advances in the role of m6A RNA modification in cancer metabolic reprogramming

2020 ◽  
Vol 10 (1) ◽  
Author(s):  
Xiu Han ◽  
Lin Wang ◽  
Qingzhen Han
Keyword(s):  
Cancer Cells ◽  
Epigenetic Modification ◽  
Metabolic Reprogramming ◽  
Regulatory Mechanisms ◽  
Rna Modification ◽  
Biological Functions ◽  
Rna Transcription ◽  
Cellular Processes ◽  
Metabolic Genes

Abstract N6-methyladenosine (m6A) modification is the most common internal modification of eukaryotic mRNA and is widely involved in many cellular processes, such as RNA transcription, splicing, nuclear transport, degradation, and translation. m6A has been shown to plays important roles in the initiation and progression of various cancers. The altered metabolic programming of cancer cells promotes their cell-autonomous proliferation and survival, leading to an indispensable hallmark of cancers. Accumulating evidence has demonstrated that this epigenetic modification exerts extensive effects on the cancer metabolic network by either directly regulating the expression of metabolic genes or modulating metabolism-associated signaling pathways. In this review, we summarized the regulatory mechanisms and biological functions of m6A and its role in cancer metabolic reprogramming.

scholarly journals The role of m6A modification in the biological functions and diseases

2021 ◽  
Vol 6 (1) ◽  
Author(s):  
Xiulin Jiang ◽  
Baiyang Liu ◽  
Zhi Nie ◽  
Lincan Duan ◽  
Qiuxia Xiong ◽  
...  
Keyword(s):  
Cancer Progression ◽  
Molecular Mechanisms ◽  
Target Genes ◽  
Rna Modification ◽  
Biological Functions ◽  
Rna Methylation ◽  
Downstream Target ◽  
Different Types ◽  
M6a Rna Methylation

AbstractN6-methyladenosine (m6A) is the most prevalent, abundant and conserved internal cotranscriptional modification in eukaryotic RNAs, especially within higher eukaryotic cells. m6A modification is modified by the m6A methyltransferases, or writers, such as METTL3/14/16, RBM15/15B, ZC3H3, VIRMA, CBLL1, WTAP, and KIAA1429, and, removed by the demethylases, or erasers, including FTO and ALKBH5. It is recognized by m6A-binding proteins YTHDF1/2/3, YTHDC1/2 IGF2BP1/2/3 and HNRNPA2B1, also known as “readers”. Recent studies have shown that m6A RNA modification plays essential role in both physiological and pathological conditions, especially in the initiation and progression of different types of human cancers. In this review, we discuss how m6A RNA methylation influences both the physiological and pathological progressions of hematopoietic, central nervous and reproductive systems. We will mainly focus on recent progress in identifying the biological functions and the underlying molecular mechanisms of m6A RNA methylation, its regulators and downstream target genes, during cancer progression in above systems. We propose that m6A RNA methylation process offer potential targets for cancer therapy in the future.

scholarly journals Regulatory Role of N6-methyladenosine (m6A) Modification in Osteosarcoma

2021 ◽  
Vol 11 ◽  
Author(s):  
Yujie Zhang ◽  
Yanyan Wang ◽  
Liwei Ying ◽  
Sifeng Tao ◽  
Mingmin Shi ◽  
...  
Keyword(s):  
Molecular Mechanism ◽  
Research Trends ◽  
Rna Modification ◽  
Future Research ◽  
Related Factors ◽  
The Past ◽  
Pathophysiological Role ◽  
Primary Bone ◽  
Non Coding Rnas

Osteosarcoma is the most common primary bone malignancy, typically occurring in childhood or adolescence. Unfortunately, the clinical outcomes of patients with osteosarcoma are usually poor because of the aggressive nature of this disease and few treatment advances in the past four decades. N6-methyladenosine (m6A) is one of the most extensive forms of RNA modification in eukaryotes found both in coding and non-coding RNAs. Accumulating evidence suggests that m6A-related factors are dysregulated in multiple osteosarcoma processes. In this review, we highlight m6A modification implicated in osteosarcoma, describing its pathophysiological role and molecular mechanism, as well as future research trends and potential clinical application in osteosarcoma.

scholarly journals Role of Main RNA Methylation in Hepatocellular Carcinoma: N6-Methyladenosine, 5-Methylcytosine, and N1-Methyladenosine

2021 ◽  
Vol 9 ◽  
Author(s):  
Yating Xu ◽  
Menggang Zhang ◽  
Qiyao Zhang ◽  
Xiao Yu ◽  
Zongzong Sun ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
Cellular Differentiation ◽  
Molecular Mechanisms ◽  
Gene Sequence ◽  
Epigenetic Modification ◽  
Biological Processes ◽  
Biological Functions ◽  
Rna Detection ◽  
Rna Methylation

RNA methylation is considered a significant epigenetic modification, a process that does not alter gene sequence but may play a necessary role in multiple biological processes, such as gene expression, genome editing, and cellular differentiation. With advances in RNA detection, various forms of RNA methylation can be found, including N6-methyladenosine (m6A), N1-methyladenosine (m1A), and 5-methylcytosine (m5C). Emerging reports confirm that dysregulation of RNA methylation gives rise to a variety of human diseases, particularly hepatocellular carcinoma. We will summarize essential regulators of RNA methylation and biological functions of these modifications in coding and noncoding RNAs. In conclusion, we highlight complex molecular mechanisms of m6A, m5C, and m1A associated with hepatocellular carcinoma and hope this review might provide therapeutic potent of RNA methylation to clinical research.

scholarly journals Hsa_circ_0110757 upregulates ITGA1 to facilitate temozolomide resistance in glioma by suppressing hsa-miR-1298-5p

2021 ◽  
Vol 12 (3) ◽  
Author(s):  
Haoyu Li ◽  
Qing Liu ◽  
Zihua Chen ◽  
Ming Wu ◽  
Chao Zhang ◽  
...  
Keyword(s):  
Tumor Invasion ◽  
High Throughput Sequencing ◽  
Myeloid Cell ◽  
Circular Rnas ◽  
Sequencing Analysis ◽  
Potential Therapeutic Target

AbstractTemozolomide (TMZ) is the internationally recognized and preferred drug for glioma chemotherapy treatment. However, TMZ resistance in glioma appears after long-term use and is an urgent problem that needs to be solved. Circular RNAs (circRNAs) are noncoding RNAs and play an important role in the pathogenesis and progression of tumors. Hsa_circ_0110757 was identified in TMZ-resistant glioma cells by high-throughput sequencing analysis and was derived from reverse splicing of myeloid cell leukemia-1 (Mcl-1) exons. The role of hsa_circ_0110757 in TMZ-resistant glioma was evaluated both in vitro and in vivo. It was found that hsa_circ_0110757 and ITGA1 are more highly expressed in TMZ-resistant glioma than in TMZ-sensitive glioma. The overexpression of hsa_circ_0110757 in glioma patients treated with TMZ was obviously associated with tumor invasion. This study indicates that hsa_circ_0110757 inhibits glioma cell apoptosis by sponging hsa-miR-1298-5p to promote ITGA1 expression. Thus, hsa_circ_0110757/hsa-miR-1298-5p/ITGA could be a potential therapeutic target for reversing the resistance of glioma to TMZ.

scholarly journals Epigenetic regulations through DNA methylation and hydroxymethylation: clues for early pregnancy in decidualization

2014 ◽  
Vol 5 (2) ◽  
pp. 95-107 ◽  
Author(s):  
Fei Gao ◽  
Sanjoy K. Das
Keyword(s):  
Gene Expression ◽  
Dna Methylation ◽  
Cell Fate ◽  
High Throughput Sequencing ◽  
Gene Expression Regulation ◽  
Epigenetic Modification ◽  
Regulation Of Gene Expression ◽  
Reproductive Organ ◽  
Epigenetic Changes ◽  
Dynamic Regulation

AbstractDNA methylation at cytosines is an important epigenetic modification that participates in gene expression regulation without changing the original DNA sequence. With the rapid progress of high-throughput sequencing techniques, whole-genome distribution of methylated cytosines and their regulatory mechanism have been revealed gradually. This has allowed the uncovering of the critical roles played by DNA methylation in the maintenance of cell pluripotency, determination of cell fate during development, and in diverse diseases. Recently, rediscovery of 5-hydroxymethylcytosine, and other types of modification on DNA, have uncovered more dynamic aspects of cell methylome regulation. The interaction of DNA methylation and other epigenetic changes remodel the chromatin structure and determine the state of gene transcription, not only permanently, but also transiently under certain stimuli. The uterus is a reproductive organ that experiences dramatic hormone stimulated changes during the estrous cycle and pregnancy, and thus provides us with a unique model for studying the dynamic regulation of epigenetic modifications. In this article, we review the current findings on the roles of genomic DNA methylation and hydroxymethylation in the regulation of gene expression, and discuss the progress of studies for these epigenetic changes in the uterus during implantation and decidualization.

Studies on the physiology of the maternal placenta in the rat

1935 ◽  
Vol 119 (812) ◽  
pp. 1-31 ◽  
Keyword(s):  
Life Span ◽  
Sex Hormones ◽  
Point Of View ◽  
Experimental Investigations ◽  
Pregnant Rat ◽  
The Past ◽  
Female Sex Hormones ◽  
Recent Advances ◽  
Important Progress

Although a great many investigators have made adequate studies on the maternal placenta from the morphogenetic point of view, little attention has so far been given to the humoral conditions which make the formation of the placenta materna possible. Experimental investigations of the problems of placental physiology have as yet been few, and leave unanswered many important questions. Which are the factors determining the life span of the placenta, and what is responsible for its ageing ? In what way are the pregnancy changes influenced by the three structures —maternal placenta, foetal placenta, and embryo—present during gestation, and what is the role of each ? Recent advances in the physiology of reproduction have made it possible to attempt the elucidation of these problems under unusually favourable conditions. Of great importance was the observation of Leo Loeb that the maternal placenta could be produced experimentally in the rodent. Furthermore, we have reported experiments which showed that the embryos could be removed from the pregnant rat and mouse without interfering with the development of either the foetal or the maternal placenta. These facts, together with the important progress of the past few years in the physiology of the female sex hormones in general, have formed the basis for our present studies, and have enabled us to elucidate some of the problems indicated above.

scholarly journals Heterochromatin remodeling by CDK12 contributes to learning in Drosophila

2015 ◽  
Vol 112 (45) ◽  
pp. 13988-13993 ◽  
Author(s):  
Lixia Pan ◽  
Wenbing Xie ◽  
Kai-Le Li ◽  
Zhihao Yang ◽  
Jiang Xu ◽  
...  
Keyword(s):  
Rna Polymerase Ii ◽  
X Chromosome ◽  
Adult Brain ◽  
Sequencing Analysis ◽  
Heterochromatin Protein 1 ◽  
Dynamic Regulation ◽  
Neuronal Genes ◽  
Neuronal Functions ◽  
Heterochromatin Structure

Dynamic regulation of chromatin structure is required to modulate the transcription of genes in eukaryotes. However, the factors that contribute to the plasticity of heterochromatin structure are elusive. Here, we report that cyclin-dependent kinase 12 (CDK12), a transcription elongation-associated RNA polymerase II (RNAPII) kinase, antagonizes heterochromatin enrichment in Drosophila chromosomes. Notably, loss of CDK12 induces the ectopic accumulation of heterochromatin protein 1 (HP1) on euchromatic arms, with a prominent enrichment on the X chromosome. Furthermore, ChIP and sequencing analysis reveals that the heterochromatin enrichment on the X chromosome mainly occurs within long genes involved in neuronal functions. Consequently, heterochromatin enrichment reduces the transcription of neuronal genes in the adult brain and results in a defect in Drosophila courtship learning. Taken together, these results define a previously unidentified role of CDK12 in controlling the epigenetic transition between euchromatin and heterochromatin and suggest a chromatin regulatory mechanism in neuronal behaviors.

scholarly journals The role m6A RNA methylation is CNS development and glioma pathogenesis

2021 ◽  
Vol 14 (1) ◽  
Author(s):  
Ting Pan ◽  
Fan Wu ◽  
Liwen Li ◽  
Shiyan Wu ◽  
Fang Zhou ◽  
...  
Keyword(s):  
Dna Methylation ◽  
Life Cycle ◽  
Crucial Role ◽  
Epigenetic Modification ◽  
Research Progress ◽  
Cns Development ◽  
Biological Functions ◽  
Rna Methylation ◽  
M6a Rna Methylation

AbstractEpigenetic abnormalities play a crucial role in many tumors, including glioma. RNA methylation occurs as an epigenetic modification similar to DNA methylation and histone modification. m6A methylation is the most common and most intensively studied RNA methylation, which can be found throughout the RNA life cycle and exert biological functions by affecting RNA metabolism. The m6A modification is primarily associated with three types of protease, which are encoded by the writer, eraser and reader genes, respectively. It has been shown that the m6A methylation has close connections with the occurrence and development of many tumors, including glioma. In this study, the concept and the research progress of m6A methylation are reviewed, especially the role of m6A methylation in glioma. Moreover, we will discuss how glioma is paving the way to the development of new therapeutic options based on the inhibition of m6A deposition.

N6-methyladenine RNA Modification (m6A): An Emerging Regulator of Metabolic Diseases

2020 ◽  
Vol 21 (11) ◽  
pp. 1056-1067 ◽  
Author(s):  
Hui Zhong ◽  
Hui-Fang Tang ◽  
Yin Kai
Keyword(s):  
Inflammatory Response ◽  
Messenger Rna ◽  
Metabolic Diseases ◽  
Rna Modification ◽  
Metabolic Dysfunction ◽  
Dynamic Regulation ◽  
Rna Methylation ◽  
New Ideas

N6-methyladenine RNA modification (m6A) is an RNA methylation modification catalyzed by methyltransferase at the 6th position nitrogen atom of adenine (A), which is the most common chemical modification of eukaryotic messenger RNA (mRNA). Recently, m6A has been found to play an important role in the dynamic regulation of RNA, which is crucial for some physiological and pathophysiological processes such as adipogenesis, cell differentiation, and the immune/inflammatory response. Metabolic diseases are a series of chronic inflammatory disorders caused by metabolic dysfunction of proteins, glucose, and lipids. Emerging studies have shown that m6A plays an important role in the process of metabolic diseases such as obesity, type 2 diabetes mellitus (T2DM) and cardiovascular diseases (CVDs) via regulation of glucose/lipid metabolism and the immune/inflammatory response. In this review, we will summarize the role of m6A in metabolic diseases, which may provide new ideas for the prevention and treatment of metabolic diseases.

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