Pub Date : 2023-08-01Epub Date: 2021-09-17DOI: 10.1016/j.gpb.2021.08.006
Zidong Liu, Xiaoxu Chen, Pengfei Zhang, Fuyuan Li, Lingkai Zhang, Xueliang Li, Tao Huang, Yi Zheng, Taiyong Yu, Tao Zhang, Wenxian Zeng, Hongzhao Lu, Yinghua Lv
Spermatogenesis is a continual process that occurs in the testes, in which diploid spermatogonial stem cells (SSCs) differentiate and generate haploid spermatozoa. This highly efficient and intricate process is orchestrated at multiple levels. N6-methyladenosine (m6A), an epigenetic modification prevalent in mRNAs, is implicated in the transcriptional regulation during spermatogenesis. However, the dynamics of m6A modification in non-rodent mammalian species remains unclear. Here, we systematically investigated the profile and role of m6A during spermatogenesis in pigs. By analyzing the transcriptomic distribution of m6A in spermatogonia, spermatocytes, and round spermatids, we identified a globally conserved m6A pattern between porcine and murine genes with spermatogenic function. We found that m6A was enriched in a group of genes that specifically encode the metabolic enzymes and regulators. In addition, transcriptomes in porcine male germ cells could be subjected to the m6A modification. Our data show that m6A plays the regulatory roles during spermatogenesis in pigs, which is similar to that in mice. Illustrations of this point are three genes (SETDB1, FOXO1, and FOXO3) that are crucial to the determination of the fate of SSCs. To the best of our knowledge, this study for the first time uncovers the expression profile and role of m6A during spermatogenesis in large animals and provides insights into the intricate transcriptional regulation underlying the lifelong male fertility in non-rodent mammalian species.
{"title":"Transcriptome-wide Dynamics of m<sup>6</sup>A mRNA Methylation During Porcine Spermatogenesis.","authors":"Zidong Liu, Xiaoxu Chen, Pengfei Zhang, Fuyuan Li, Lingkai Zhang, Xueliang Li, Tao Huang, Yi Zheng, Taiyong Yu, Tao Zhang, Wenxian Zeng, Hongzhao Lu, Yinghua Lv","doi":"10.1016/j.gpb.2021.08.006","DOIUrl":"10.1016/j.gpb.2021.08.006","url":null,"abstract":"<p><p>Spermatogenesis is a continual process that occurs in the testes, in which diploid spermatogonial stem cells (SSCs) differentiate and generate haploid spermatozoa. This highly efficient and intricate process is orchestrated at multiple levels. N<sup>6</sup>-methyladenosine (m<sup>6</sup>A), an epigenetic modification prevalent in mRNAs, is implicated in the transcriptional regulation during spermatogenesis. However, the dynamics of m<sup>6</sup>A modification in non-rodent mammalian species remains unclear. Here, we systematically investigated the profile and role of m<sup>6</sup>A during spermatogenesis in pigs. By analyzing the transcriptomic distribution of m<sup>6</sup>A in spermatogonia, spermatocytes, and round spermatids, we identified a globally conserved m<sup>6</sup>A pattern between porcine and murine genes with spermatogenic function. We found that m<sup>6</sup>A was enriched in a group of genes that specifically encode the metabolic enzymes and regulators. In addition, transcriptomes in porcine male germ cells could be subjected to the m<sup>6</sup>A modification. Our data show that m<sup>6</sup>A plays the regulatory roles during spermatogenesis in pigs, which is similar to that in mice. Illustrations of this point are three genes (SETDB1, FOXO1, and FOXO3) that are crucial to the determination of the fate of SSCs. To the best of our knowledge, this study for the first time uncovers the expression profile and role of m<sup>6</sup>A during spermatogenesis in large animals and provides insights into the intricate transcriptional regulation underlying the lifelong male fertility in non-rodent mammalian species.</p>","PeriodicalId":12528,"journal":{"name":"Genomics, Proteomics & Bioinformatics","volume":null,"pages":null},"PeriodicalIF":11.5,"publicationDate":"2023-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10787014/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"39435772","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2023-08-01Epub Date: 2022-09-09DOI: 10.1016/j.gpb.2022.09.001
Bowen Song, Daiyun Huang, Yuxin Zhang, Zhen Wei, Jionglong Su, João Pedro de Magalhães, Daniel J Rigden, Jia Meng, Kunqi Chen
As the most pervasive epigenetic marker present on mRNAs and long non-coding RNAs (lncRNAs), N6-methyladenosine (m6A) RNA methylation has been shown to participate in essential biological processes. Recent studies have revealed the distinct patterns of m6A methylome across human tissues, and a major challenge remains in elucidating the tissue-specific presence and circuitry of m6A methylation. We present here a comprehensive online platform, m6A-TSHub, for unveiling the context-specific m6A methylation and genetic mutations that potentially regulate m6A epigenetic mark. m6A-TSHub consists of four core components, including (1) m6A-TSDB, a comprehensive database of 184,554 functionally annotated m6A sites derived from 23 human tissues and 499,369 m6A sites from 25 tumor conditions, respectively; (2) m6A-TSFinder, a web server for high-accuracy prediction of m6A methylation sites within a specific tissue from RNA sequences, which was constructed using multi-instance deep neural networks with gated attention; (3) m6A-TSVar, a web server for assessing the impact of genetic variants on tissue-specific m6A RNA modifications; and (4) m6A-CAVar, a database of 587,983 The Cancer Genome Atlas (TCGA) cancer mutations (derived from 27 cancer types) that were predicted to affect m6A modifications in the primary tissue of cancers. The database should make a useful resource for studying the m6A methylome and the genetic factors of epitranscriptome disturbance in a specific tissue (or cancer type). m6A-TSHub is accessible at www.xjtlu.edu.cn/biologicalsciences/m6ats.
{"title":"m6A-TSHub: Unveiling the Context-specific m<sup>6</sup>A Methylation and m<sup>6</sup>A-affecting Mutations in 23 Human Tissues.","authors":"Bowen Song, Daiyun Huang, Yuxin Zhang, Zhen Wei, Jionglong Su, João Pedro de Magalhães, Daniel J Rigden, Jia Meng, Kunqi Chen","doi":"10.1016/j.gpb.2022.09.001","DOIUrl":"10.1016/j.gpb.2022.09.001","url":null,"abstract":"<p><p>As the most pervasive epigenetic marker present on mRNAs and long non-coding RNAs (lncRNAs), N<sup>6</sup>-methyladenosine (m<sup>6</sup>A) RNA methylation has been shown to participate in essential biological processes. Recent studies have revealed the distinct patterns of m<sup>6</sup>A methylome across human tissues, and a major challenge remains in elucidating the tissue-specific presence and circuitry of m<sup>6</sup>A methylation. We present here a comprehensive online platform, m6A-TSHub, for unveiling the context-specific m<sup>6</sup>A methylation and genetic mutations that potentially regulate m<sup>6</sup>A epigenetic mark. m6A-TSHub consists of four core components, including (1) m6A-TSDB, a comprehensive database of 184,554 functionally annotated m<sup>6</sup>A sites derived from 23 human tissues and 499,369 m<sup>6</sup>A sites from 25 tumor conditions, respectively; (2) m6A-TSFinder, a web server for high-accuracy prediction of m<sup>6</sup>A methylation sites within a specific tissue from RNA sequences, which was constructed using multi-instance deep neural networks with gated attention; (3) m6A-TSVar, a web server for assessing the impact of genetic variants on tissue-specific m<sup>6</sup>A RNA modifications; and (4) m6A-CAVar, a database of 587,983 The Cancer Genome Atlas (TCGA) cancer mutations (derived from 27 cancer types) that were predicted to affect m<sup>6</sup>A modifications in the primary tissue of cancers. The database should make a useful resource for studying the m<sup>6</sup>A methylome and the genetic factors of epitranscriptome disturbance in a specific tissue (or cancer type). m6A-TSHub is accessible at www.xjtlu.edu.cn/biologicalsciences/m6ats.</p>","PeriodicalId":12528,"journal":{"name":"Genomics, Proteomics & Bioinformatics","volume":null,"pages":null},"PeriodicalIF":11.5,"publicationDate":"2023-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10787194/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"33464009","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2023-08-01Epub Date: 2022-07-11DOI: 10.1016/j.gpb.2022.04.009
Yafen Wang, Xiang Zhou
N6-methyladenine (m6A) is the most abundant RNA modification in mammalian messenger RNAs (mRNAs), which participates in and regulates many important biological activities, such as tissue development and stem cell differentiation. Due to an improved understanding of m6A, researchers have discovered that the biological function of m6A can be linked to many stages of mRNA metabolism and that m6A can regulate a variety of complex biological processes. In addition to its location on mammalian mRNAs, m6A has been identified on viral transcripts. m6A also plays important roles in the life cycle of many viruses and in viral replication in host cells. In this review, we briefly introduce the detection methods of m6A, the m6A-related proteins, and the functions of m6A. We also summarize the effects of m6A-related proteins on viral replication and infection. We hope that this review provides researchers with some insights for elucidating the complex mechanisms of the epitranscriptome related to viruses, and provides information for further study of the mechanisms of other modified nucleobases acting on processes such as viral replication. We also anticipate that this review can stimulate collaborative research from different fields, such as chemistry, biology, and medicine, and promote the development of antiviral drugs and vaccines.
{"title":"N<sup>6</sup>-methyladenosine and Its Implications in Viruses.","authors":"Yafen Wang, Xiang Zhou","doi":"10.1016/j.gpb.2022.04.009","DOIUrl":"10.1016/j.gpb.2022.04.009","url":null,"abstract":"<p><p>N<sup>6</sup>-methyladenine (m<sup>6</sup>A) is the most abundant RNA modification in mammalian messenger RNAs (mRNAs), which participates in and regulates many important biological activities, such as tissue development and stem cell differentiation. Due to an improved understanding of m<sup>6</sup>A, researchers have discovered that the biological function of m<sup>6</sup>A can be linked to many stages of mRNA metabolism and that m<sup>6</sup>A can regulate a variety of complex biological processes. In addition to its location on mammalian mRNAs, m<sup>6</sup>A has been identified on viral transcripts. m<sup>6</sup>A also plays important roles in the life cycle of many viruses and in viral replication in host cells. In this review, we briefly introduce the detection methods of m<sup>6</sup>A, the m<sup>6</sup>A-related proteins, and the functions of m<sup>6</sup>A. We also summarize the effects of m<sup>6</sup>A-related proteins on viral replication and infection. We hope that this review provides researchers with some insights for elucidating the complex mechanisms of the epitranscriptome related to viruses, and provides information for further study of the mechanisms of other modified nucleobases acting on processes such as viral replication. We also anticipate that this review can stimulate collaborative research from different fields, such as chemistry, biology, and medicine, and promote the development of antiviral drugs and vaccines.</p>","PeriodicalId":12528,"journal":{"name":"Genomics, Proteomics & Bioinformatics","volume":null,"pages":null},"PeriodicalIF":11.5,"publicationDate":"2023-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10787122/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"40603915","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Serine/arginine-rich splicing factor 7 (SRSF7), a known splicing factor, has been revealed to play oncogenic roles in multiple cancers. However, the mechanisms underlying its oncogenic roles have not been well addressed. Here, based on N6-methyladenosine (m6A) co-methylation network analysis across diverse cell lines, we find that the gene expression of SRSF7 is positively correlated with glioblastoma (GBM) cell-specific m6A methylation. We then indicate that SRSF7 is a novel m6A regulator, which specifically facilitates the m6A methylation near its binding sites on the mRNAs involved in cell proliferation and migration, through recruiting the methyltransferase complex. Moreover, SRSF7 promotes the proliferation and migration of GBM cells largely dependent on the presence of the m6A methyltransferase. The two m6A sites on the mRNA for PDZ-binding kinase (PBK) are regulated by SRSF7 and partially mediate the effects of SRSF7 in GBM cells through recognition by insulin-like growth factor 2 mRNA-binding protein 2 (IGF2BP2). Together, our discovery reveals a novel role of SRSF7 in regulating m6A and validates the presence and functional importance of temporal- and spatial-specific regulation of m6A mediated by RNA-binding proteins (RBPs).
{"title":"Specific Regulation of m<sup>6</sup>A by SRSF7 Promotes the Progression of Glioblastoma.","authors":"Yixian Cun, Sanqi An, Haiqing Zheng, Jing Lan, Wenfang Chen, Wanjun Luo, Chengguo Yao, Xincheng Li, Xiang Huang, Xiang Sun, Zehong Wu, Yameng Hu, Ziwen Li, Shuxia Zhang, Geyan Wu, Meisongzhu Yang, Miaoling Tang, Ruyuan Yu, Xinyi Liao, Guicheng Gao, Wei Zhao, Jinkai Wang, Jun Li","doi":"10.1016/j.gpb.2021.11.001","DOIUrl":"10.1016/j.gpb.2021.11.001","url":null,"abstract":"<p><p>Serine/arginine-rich splicing factor 7 (SRSF7), a known splicing factor, has been revealed to play oncogenic roles in multiple cancers. However, the mechanisms underlying its oncogenic roles have not been well addressed. Here, based on N<sup>6</sup>-methyladenosine (m<sup>6</sup>A) co-methylation network analysis across diverse cell lines, we find that the gene expression of SRSF7 is positively correlated with glioblastoma (GBM) cell-specific m<sup>6</sup>A methylation. We then indicate that SRSF7 is a novel m<sup>6</sup>A regulator, which specifically facilitates the m<sup>6</sup>A methylation near its binding sites on the mRNAs involved in cell proliferation and migration, through recruiting the methyltransferase complex. Moreover, SRSF7 promotes the proliferation and migration of GBM cells largely dependent on the presence of the m<sup>6</sup>A methyltransferase. The two m<sup>6</sup>A sites on the mRNA for PDZ-binding kinase (PBK) are regulated by SRSF7 and partially mediate the effects of SRSF7 in GBM cells through recognition by insulin-like growth factor 2 mRNA-binding protein 2 (IGF2BP2). Together, our discovery reveals a novel role of SRSF7 in regulating m<sup>6</sup>A and validates the presence and functional importance of temporal- and spatial-specific regulation of m<sup>6</sup>A mediated by RNA-binding proteins (RBPs).</p>","PeriodicalId":12528,"journal":{"name":"Genomics, Proteomics & Bioinformatics","volume":null,"pages":null},"PeriodicalIF":11.5,"publicationDate":"2023-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10787126/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"39875095","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2023-08-01Epub Date: 2022-11-24DOI: 10.1016/j.gpb.2022.10.006
Boyang Shi, Ke An, Yueqin Wang, Yuhan Fei, Caixia Guo, Qiangfeng Cliff Zhang, Yun-Gui Yang, Xin Tian, Quancheng Kan
Epidermal growth factor receptor-tyrosine kinase inhibitors (EGFR-TKIs) positively affect the initial control of non-small cell lung cancer (NSCLC). Rapidly acquired resistance to EGFR-TKIs is a major hurdle in successful treatment. However, the mechanisms that control the resistance of EGFR-TKIs remain largely unknown. RNA structures have widespread and crucial functions in many biological regulations; however, the functions of RNA structures in regulating cancer drug resistance remain unclear. Here, the psoralen analysis of RNA interactions and structures (PARIS) method is used to establish the higher-order RNA structure maps of EGFR-TKIs-resistant and -sensitive cells of NSCLC. Our results show that RNA structural regions are enriched in untranslated regions (UTRs) and correlate with translation efficiency (TE). Moreover, yrdC N6-threonylcarbamoyltransferase domain containing (YRDC) promotes resistance to EGFR-TKIs. RNA structure formation in YRDC 3' UTR suppresses embryonic lethal abnormal vision-like 1 (ELAVL1) binding, leading to EGFR-TKI sensitivity by impairing YRDC translation. A potential therapeutic strategy for cancer treatment is provided using antisense oligonucleotide (ASO) to perturb the interaction between RNA and protein. Our study reveals an unprecedented mechanism through which the RNA structure switch modulates EGFR-TKI resistance by controlling YRDC mRNA translation in an ELAVL1-dependent manner.
表皮生长因子受体酪氨酸激酶抑制剂(EGFR-TKIs)对非小细胞肺癌(NSCLC)的初始控制率有正向影响。对EGFR-TKI的快速获得性耐药是成功治疗的主要障碍。然而,控制EGFR-TKI耐药性的机制在很大程度上仍然未知。RNA结构在许多生物调控中具有广泛而关键的功能;然而,RNA结构在调节癌症耐药中的功能尚不清楚。本研究采用psoralen analysis of RNA interactions and structures (PARIS)方法建立NSCLC egfr - tki耐药和敏感细胞的高阶RNA结构图。我们的研究结果表明,RNA结构区在非翻译区(UTRs)中富集,并与翻译效率(TE)相关。此外,yrdC含有n6 -苏酰基氨基甲酰转移酶结构域(yrdC)促进对EGFR-TKI的抗性。YRDC 3' UTR中的RNA结构形成抑制胚胎致死性异视样1 (ELAVL1)结合,通过损害YRDC翻译导致EGFR-TKI敏感性。利用反义寡核苷酸(ASO)干扰RNA与蛋白质之间的相互作用,提供了一种潜在的癌症治疗策略。我们的研究揭示了一种前所未有的机制,通过RNA结构开关以依赖于elavl1的方式控制YRDC mRNA的翻译,从而调节EGFR-TKI耐药性。
{"title":"RNA Structural Dynamics Modulate EGFR-TKI Resistance Through Controlling YRDC Translation in NSCLC Cells.","authors":"Boyang Shi, Ke An, Yueqin Wang, Yuhan Fei, Caixia Guo, Qiangfeng Cliff Zhang, Yun-Gui Yang, Xin Tian, Quancheng Kan","doi":"10.1016/j.gpb.2022.10.006","DOIUrl":"10.1016/j.gpb.2022.10.006","url":null,"abstract":"<p><p>Epidermal growth factor receptor-tyrosine kinase inhibitors (EGFR-TKIs) positively affect the initial control of non-small cell lung cancer (NSCLC). Rapidly acquired resistance to EGFR-TKIs is a major hurdle in successful treatment. However, the mechanisms that control the resistance of EGFR-TKIs remain largely unknown. RNA structures have widespread and crucial functions in many biological regulations; however, the functions of RNA structures in regulating cancer drug resistance remain unclear. Here, the psoralen analysis of RNA interactions and structures (PARIS) method is used to establish the higher-order RNA structure maps of EGFR-TKIs-resistant and -sensitive cells of NSCLC. Our results show that RNA structural regions are enriched in untranslated regions (UTRs) and correlate with translation efficiency (TE). Moreover, yrdC N<sup>6</sup>-threonylcarbamoyltransferase domain containing (YRDC) promotes resistance to EGFR-TKIs. RNA structure formation in YRDC 3' UTR suppresses embryonic lethal abnormal vision-like 1 (ELAVL1) binding, leading to EGFR-TKI sensitivity by impairing YRDC translation. A potential therapeutic strategy for cancer treatment is provided using antisense oligonucleotide (ASO) to perturb the interaction between RNA and protein. Our study reveals an unprecedented mechanism through which the RNA structure switch modulates EGFR-TKI resistance by controlling YRDC mRNA translation in an ELAVL1-dependent manner.</p>","PeriodicalId":12528,"journal":{"name":"Genomics, Proteomics & Bioinformatics","volume":null,"pages":null},"PeriodicalIF":11.5,"publicationDate":"2023-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10787121/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"40722476","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2023-08-01Epub Date: 2022-01-25DOI: 10.1016/j.gpb.2022.01.003
Shuai Chen, Jinyang Zhang, Fangqing Zhao
Stress granules (SGs) are cytoplasmic ribonucleoprotein assemblies formed under stress conditions and are related to various biological processes and human diseases. Previous studies have reported the regulatory role of some proteins and linear RNAs in SG assembly. However, the relationship between circular RNAs (circRNAs) and SGs has not been discovered. Here, we screened both linear RNAs and circRNAs in SGs using improved total RNA sequencing of purified SG cores in mammalian cells and identified circular transcripts specifically localized in SGs. circRNAs with higher SG-related RNA-binding protein (RBP) binding abilities are more likely to be enriched in SGs. Furthermore, some SG-enriched circRNAs are differentially expressed in hepatocellular carcinoma (HCC) and adjacent tissues. These results suggest the regulatory role of circRNAs in SG formation and provide insights into the biological function of circRNAs and SGs in HCC.
{"title":"Screening Linear and Circular RNA Transcripts from Stress Granules.","authors":"Shuai Chen, Jinyang Zhang, Fangqing Zhao","doi":"10.1016/j.gpb.2022.01.003","DOIUrl":"10.1016/j.gpb.2022.01.003","url":null,"abstract":"<p><p>Stress granules (SGs) are cytoplasmic ribonucleoprotein assemblies formed under stress conditions and are related to various biological processes and human diseases. Previous studies have reported the regulatory role of some proteins and linear RNAs in SG assembly. However, the relationship between circular RNAs (circRNAs) and SGs has not been discovered. Here, we screened both linear RNAs and circRNAs in SGs using improved total RNA sequencing of purified SG cores in mammalian cells and identified circular transcripts specifically localized in SGs. circRNAs with higher SG-related RNA-binding protein (RBP) binding abilities are more likely to be enriched in SGs. Furthermore, some SG-enriched circRNAs are differentially expressed in hepatocellular carcinoma (HCC) and adjacent tissues. These results suggest the regulatory role of circRNAs in SG formation and provide insights into the biological function of circRNAs and SGs in HCC.</p>","PeriodicalId":12528,"journal":{"name":"Genomics, Proteomics & Bioinformatics","volume":null,"pages":null},"PeriodicalIF":11.5,"publicationDate":"2023-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10787114/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"39741400","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2023-08-01Epub Date: 2022-08-08DOI: 10.1016/j.gpb.2022.07.006
Peng Yu, Siting Zhou, Yan Gao, Yu Liang, Wenbing Guo, Dan Ohtan Wang, Shuaiwen Ding, Shuibin Lin, Jinkai Wang, Yixian Cun
Although the function of tRNAs in the translational process is well established, it remains controversial whether tRNA abundance is tightly associated with translational efficiency (TE) in mammals. Moreover, how critically the expression of tRNAs contributes to the establishment of tissue-specific proteomes in mammals has not been well addressed. Here, we measured both tRNA expression using demethylase-tRNA sequencing (DM-tRNA-seq) and TE of mRNAs using ribosome-tagging sequencing (RiboTag-seq) in the brain, heart, and testis of mice. Remarkable variation in the expression of tRNA isodecoders was observed among different tissues. When the statistical effect of isodecoder-grouping on reducing variations is considered through permutating the anticodons, we observed an expected reduction in the variation of anticodon expression across all samples, an unexpected smaller variation of anticodon usage bias, and an unexpected larger variation of tRNA isotype expression at amino acid level. Regardless of whether or not they share the same anticodons, the isodecoders encoding the same amino acids are co-expressed across different tissues. Based on the expression of tRNAs and the TE of mRNAs, we find that the tRNA adaptation index (tAI) and TE are significantly correlated in the same tissues but not between tissues; and tRNA expression and the amino acid composition of translating peptides are positively correlated in the same tissues but not between tissues. We therefore hypothesize that the tissue-specific expression of tRNAs might be due to post-transcriptional mechanisms. This study provides a resource for tRNA and translation studies, as well as novel insights into the dynamics of tRNAs and their roles in translational regulation.
{"title":"Dynamic Landscapes of tRNA Transcriptomes and Translatomes in Diverse Mouse Tissues.","authors":"Peng Yu, Siting Zhou, Yan Gao, Yu Liang, Wenbing Guo, Dan Ohtan Wang, Shuaiwen Ding, Shuibin Lin, Jinkai Wang, Yixian Cun","doi":"10.1016/j.gpb.2022.07.006","DOIUrl":"10.1016/j.gpb.2022.07.006","url":null,"abstract":"<p><p>Although the function of tRNAs in the translational process is well established, it remains controversial whether tRNA abundance is tightly associated with translational efficiency (TE) in mammals. Moreover, how critically the expression of tRNAs contributes to the establishment of tissue-specific proteomes in mammals has not been well addressed. Here, we measured both tRNA expression using demethylase-tRNA sequencing (DM-tRNA-seq) and TE of mRNAs using ribosome-tagging sequencing (RiboTag-seq) in the brain, heart, and testis of mice. Remarkable variation in the expression of tRNA isodecoders was observed among different tissues. When the statistical effect of isodecoder-grouping on reducing variations is considered through permutating the anticodons, we observed an expected reduction in the variation of anticodon expression across all samples, an unexpected smaller variation of anticodon usage bias, and an unexpected larger variation of tRNA isotype expression at amino acid level. Regardless of whether or not they share the same anticodons, the isodecoders encoding the same amino acids are co-expressed across different tissues. Based on the expression of tRNAs and the TE of mRNAs, we find that the tRNA adaptation index (tAI) and TE are significantly correlated in the same tissues but not between tissues; and tRNA expression and the amino acid composition of translating peptides are positively correlated in the same tissues but not between tissues. We therefore hypothesize that the tissue-specific expression of tRNAs might be due to post-transcriptional mechanisms. This study provides a resource for tRNA and translation studies, as well as novel insights into the dynamics of tRNAs and their roles in translational regulation.</p>","PeriodicalId":12528,"journal":{"name":"Genomics, Proteomics & Bioinformatics","volume":null,"pages":null},"PeriodicalIF":11.5,"publicationDate":"2023-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10787195/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"40601125","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
The epitranscriptomic mark N6-methyladenosine (m6A), which is the predominant internal modification in RNA, is important for plant responses to diverse stresses. Multiple environmental stresses caused by the tea-withering process can greatly influence the accumulation of specialized metabolites and the formation of tea flavor. However, the effects of the m6A-mediated regulatory mechanism on flavor-related metabolic pathways in tea leaves remain relatively uncharacterized. We performed an integrated RNA methylome and transcriptome analysis to explore the m6A-mediated regulatory mechanism and its effects on flavonoid and terpenoid metabolism in tea (Camellia sinensis) leaves under solar-withering conditions. Dynamic changes in global m6A level in tea leaves were mainly controlled by two m6A erasers (CsALKBH4A and CsALKBH4B) during solar-withering treatments. Differentially methylated peak-associated genes following solar-withering treatments with different shading rates were assigned to terpenoid biosynthesis and spliceosome pathways. Further analyses indicated that CsALKBH4-driven RNA demethylation can directly affect the accumulation of volatile terpenoids by mediating the stability and abundance of terpenoid biosynthesis-related transcripts and also indirectly influence the flavonoid, catechin, and theaflavin contents by triggering alternative splicing-mediated regulation. Our findings revealed a novel layer of epitranscriptomic gene regulation in tea flavor-related metabolic pathways and established a link between the m6A-mediated regulatory mechanism and the formation of tea flavor under solar-withering conditions.
{"title":"RNA Methylome Reveals the m<sup>6</sup>A-mediated Regulation of Flavor Metabolites in Tea Leaves under Solar-withering.","authors":"Chen Zhu, Shuting Zhang, Chengzhe Zhou, Caiyun Tian, Biying Shi, Kai Xu, Linjie Huang, Yun Sun, Yuling Lin, Zhongxiong Lai, Yuqiong Guo","doi":"10.1016/j.gpb.2023.02.003","DOIUrl":"10.1016/j.gpb.2023.02.003","url":null,"abstract":"<p><p>The epitranscriptomic mark N<sup>6</sup>-methyladenosine (m<sup>6</sup>A), which is the predominant internal modification in RNA, is important for plant responses to diverse stresses. Multiple environmental stresses caused by the tea-withering process can greatly influence the accumulation of specialized metabolites and the formation of tea flavor. However, the effects of the m<sup>6</sup>A-mediated regulatory mechanism on flavor-related metabolic pathways in tea leaves remain relatively uncharacterized. We performed an integrated RNA methylome and transcriptome analysis to explore the m<sup>6</sup>A-mediated regulatory mechanism and its effects on flavonoid and terpenoid metabolism in tea (Camellia sinensis) leaves under solar-withering conditions. Dynamic changes in global m<sup>6</sup>A level in tea leaves were mainly controlled by two m<sup>6</sup>A erasers (CsALKBH4A and CsALKBH4B) during solar-withering treatments. Differentially methylated peak-associated genes following solar-withering treatments with different shading rates were assigned to terpenoid biosynthesis and spliceosome pathways. Further analyses indicated that CsALKBH4-driven RNA demethylation can directly affect the accumulation of volatile terpenoids by mediating the stability and abundance of terpenoid biosynthesis-related transcripts and also indirectly influence the flavonoid, catechin, and theaflavin contents by triggering alternative splicing-mediated regulation. Our findings revealed a novel layer of epitranscriptomic gene regulation in tea flavor-related metabolic pathways and established a link between the m<sup>6</sup>A-mediated regulatory mechanism and the formation of tea flavor under solar-withering conditions.</p>","PeriodicalId":12528,"journal":{"name":"Genomics, Proteomics & Bioinformatics","volume":null,"pages":null},"PeriodicalIF":11.5,"publicationDate":"2023-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10787128/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10737666","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2023-08-01Epub Date: 2022-09-30DOI: 10.1016/j.gpb.2022.09.007
Dan Song, Ke An, Wenlong Zhai, Luyao Feng, Yingjie Xu, Ran Sun, Yueqin Wang, Yun-Gui Yang, Quancheng Kan, Xin Tian
RNA modifications affect many biological processes and physiological diseases. The 5-methylcytosine (m5C) modification regulates the progression of multiple tumors. However, its characteristics and functions in hepatocellular carcinoma (HCC) remain largely unknown. Here, we found that HCC tissues had a higher m5C methylation level than the adjacent normal tissues. Transcriptome analysis revealed that the hypermethylated genes mainly participated in the phosphokinase signaling pathways, such as the Ras and PI3K-Akt pathways. The m5C methyltransferase NSUN2 was highly expressed in HCC tissues. Interestingly, the expression of many genes was positively correlated with the expression of NSUN2, including GRB2, RNF115, AATF, ADAM15, RTN3, and HDGF. Real-time PCR assays further revealed that the expression of the mRNAs of GRB2, RNF115, and AATF decreased significantly with the down-regulation of NSUN2 expression in HCC cells. Furthermore, NSUN2 could regulate the cellular sensitivity of HCC cells to sorafenib via modulating the Ras signaling pathway. Moreover, knocking down NSUN2 caused cell cycle arrest. Taken together, our study demonstrates the vital role of NSUN2 in the progression of HCC.
{"title":"NSUN2-mediated mRNA m<sup>5</sup>C Modification Regulates the Progression of Hepatocellular Carcinoma.","authors":"Dan Song, Ke An, Wenlong Zhai, Luyao Feng, Yingjie Xu, Ran Sun, Yueqin Wang, Yun-Gui Yang, Quancheng Kan, Xin Tian","doi":"10.1016/j.gpb.2022.09.007","DOIUrl":"10.1016/j.gpb.2022.09.007","url":null,"abstract":"<p><p>RNA modifications affect many biological processes and physiological diseases. The 5-methylcytosine (m<sup>5</sup>C) modification regulates the progression of multiple tumors. However, its characteristics and functions in hepatocellular carcinoma (HCC) remain largely unknown. Here, we found that HCC tissues had a higher m<sup>5</sup>C methylation level than the adjacent normal tissues. Transcriptome analysis revealed that the hypermethylated genes mainly participated in the phosphokinase signaling pathways, such as the Ras and PI3K-Akt pathways. The m<sup>5</sup>C methyltransferase NSUN2 was highly expressed in HCC tissues. Interestingly, the expression of many genes was positively correlated with the expression of NSUN2, including GRB2, RNF115, AATF, ADAM15, RTN3, and HDGF. Real-time PCR assays further revealed that the expression of the mRNAs of GRB2, RNF115, and AATF decreased significantly with the down-regulation of NSUN2 expression in HCC cells. Furthermore, NSUN2 could regulate the cellular sensitivity of HCC cells to sorafenib via modulating the Ras signaling pathway. Moreover, knocking down NSUN2 caused cell cycle arrest. Taken together, our study demonstrates the vital role of NSUN2 in the progression of HCC.</p>","PeriodicalId":12528,"journal":{"name":"Genomics, Proteomics & Bioinformatics","volume":null,"pages":null},"PeriodicalIF":11.5,"publicationDate":"2023-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10787115/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"40388031","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
After implantation, complex and highly specialized molecular events render functionally distinct organ formation, whereas how the epigenome shapes organ-specific development remains to be fully elucidated. Here, nano-hmC-Seal, RNA bisulfite sequencing (RNA-BisSeq), and RNA sequencing (RNA-Seq) were performed, and the first multilayer landscapes of DNA 5-hydroxymethylcytosine (5hmC) and RNA 5-methylcytosine (m5C) epigenomes were obtained in the heart, kidney, liver, and lung of the human foetuses at 13-28 weeks with 123 samples in total. We identified 70,091 and 503 organ- and stage-specific differentially hydroxymethylated regions (DhMRs) and m5C-modified mRNAs, respectively. The key transcription factors (TFs), T-box transcription factor 20 (TBX20), paired box 8 (PAX8), krueppel-like factor 1 (KLF1), transcription factor 21 (TCF21), and CCAAT enhancer binding protein beta (CEBPB), specifically contribute to the formation of distinct organs at different stages. Additionally, 5hmC-enriched Alu elements may participate in the regulation of expression of TF-targeted genes. Our integrated studies reveal a putative essential link between DNA modification and RNA methylation, and illustrate the epigenetic maps during human foetal organogenesis, which provide a foundation for for an in-depth understanding of the epigenetic mechanisms underlying early development and birth defects.
{"title":"Dynamic DNA 5-hydroxylmethylcytosine and RNA 5-methycytosine Reprogramming During Early Human Development.","authors":"Xiao Han, Jia Guo, Mengke Wang, Nan Zhang, Jie Ren, Ying Yang, Xu Chi, Yusheng Chen, Huan Yao, Yong-Liang Zhao, Yun-Gui Yang, Yingpu Sun, Jiawei Xu","doi":"10.1016/j.gpb.2022.05.005","DOIUrl":"10.1016/j.gpb.2022.05.005","url":null,"abstract":"<p><p>After implantation, complex and highly specialized molecular events render functionally distinct organ formation, whereas how the epigenome shapes organ-specific development remains to be fully elucidated. Here, nano-hmC-Seal, RNA bisulfite sequencing (RNA-BisSeq), and RNA sequencing (RNA-Seq) were performed, and the first multilayer landscapes of DNA 5-hydroxymethylcytosine (5hmC) and RNA 5-methylcytosine (m<sup>5</sup>C) epigenomes were obtained in the heart, kidney, liver, and lung of the human foetuses at 13-28 weeks with 123 samples in total. We identified 70,091 and 503 organ- and stage-specific differentially hydroxymethylated regions (DhMRs) and m<sup>5</sup>C-modified mRNAs, respectively. The key transcription factors (TFs), T-box transcription factor 20 (TBX20), paired box 8 (PAX8), krueppel-like factor 1 (KLF1), transcription factor 21 (TCF21), and CCAAT enhancer binding protein beta (CEBPB), specifically contribute to the formation of distinct organs at different stages. Additionally, 5hmC-enriched Alu elements may participate in the regulation of expression of TF-targeted genes. Our integrated studies reveal a putative essential link between DNA modification and RNA methylation, and illustrate the epigenetic maps during human foetal organogenesis, which provide a foundation for for an in-depth understanding of the epigenetic mechanisms underlying early development and birth defects.</p>","PeriodicalId":12528,"journal":{"name":"Genomics, Proteomics & Bioinformatics","volume":null,"pages":null},"PeriodicalIF":11.5,"publicationDate":"2023-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10787118/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"41390959","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}