Pub Date : 2023-08-01DOI: 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 m5C 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":"<div><div>RNA modifications affect many biological processes and physiological diseases. The <strong>5-methylcytosine</strong> (m<sup>5</sup>C) modification regulates the progression of multiple tumors. However, its characteristics and functions in <strong>hepatocellular carcinoma</strong> (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 <strong>NSUN2</strong> was highly expressed in HCC tissues. Interestingly, the expression of many genes was positively correlated with the expression of <em>NSUN2</em>, including <em>GRB2</em>, <em>RNF115</em>, <em>AATF</em>, <em>ADAM15</em>, <em>RTN3</em>, and <em>HDGF</em>. Real-time PCR assays further revealed that the expression of the mRNAs of <em>GRB2</em>, <em>RNF115</em>, and <em>AATF</em> decreased significantly with the down-regulation of <em>NSUN2</em> expression in HCC cells. Furthermore, NSUN2 could regulate the cellular sensitivity of HCC cells to <strong>sorafenib</strong> via modulating the Ras signaling pathway. Moreover, knocking down <em>NSUN2</em> caused cell cycle arrest. Taken together, our study demonstrates the vital role of NSUN2 in the progression of HCC.</div></div>","PeriodicalId":12528,"journal":{"name":"Genomics, Proteomics & Bioinformatics","volume":"21 4","pages":"Pages 823-833"},"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}
Pub Date : 2023-08-01DOI: 10.1016/j.gpb.2022.05.005
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
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 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":"<div><div>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 an in-depth understanding of the epigenetic mechanisms underlying early development and birth defects.</div></div>","PeriodicalId":12528,"journal":{"name":"Genomics, Proteomics & Bioinformatics","volume":"21 4","pages":"Pages 805-822"},"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}
Pub Date : 2023-08-01DOI: 10.1016/j.gpb.2023.02.003
Chen Zhu , Shuting Zhang , Chengzhe Zhou , Caiyun Tian , Biying Shi , Kai Xu , Linjie Huang , Yun Sun , Yuling Lin , Zhongxiong Lai , Yuqiong Guo
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 m6A-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":"<div><div>The epitranscriptomic mark <em>N</em><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-<strong>withering</strong> 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 (<em>Camellia sinensis</em>) 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.</div></div>","PeriodicalId":12528,"journal":{"name":"Genomics, Proteomics & Bioinformatics","volume":"21 4","pages":"Pages 769-787"},"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 : 2023-08-01DOI: 10.1016/j.gpb.2022.12.002
Lorane Le Franc , Bruno Petton , Pascal Favrel , Guillaume Rivière
The N6-methylation of RNA adenosines (N6-methyladenosine, m6A) is an important regulator of gene expression with critical implications in vertebrate and insect development. However, the developmental significance of epitranscriptomes in lophotrochozoan organisms remains unknown. Using methylated RNA immunoprecipitation sequencing (MeRIP-seq), we generated transcriptome-wide m6A-RNA methylomes covering the entire development of the oyster from oocytes to juveniles. Oyster RNA classes display specific m6A signatures, with messenger RNAs (mRNAs) and long non-coding RNAs (lncRNAs) exhibiting distinct profiles and being highly methylated compared to transposable element (TE) transcripts. Epitranscriptomes are dynamic and correspond to the chronological steps of development (cleavage, gastrulation, organogenesis, and metamorphosis), with minimal mRNA and lncRNA methylation at the morula stage followed by a global increase. mRNA m6A levels are correlated with transcript levels, and shifts in methylation profiles correspond to expression kinetics. Differentially methylated transcripts cluster according to embryo-larval stages and bear the corresponding developmental functions (cell division, signal transduction, morphogenesis, and cell differentiation). The m6A level of TE transcripts is also regulated and peaks during the gastrulation. We demonstrate that m6A-RNA methylomes are dynamic and associated with gene expression regulation during oyster development. The putative epitranscriptome implication in the cleavage, maternal-to-zygotic transition, and cell differentiation in a lophotrochozoan model brings new insights into the control and evolution of developmental processes.
{"title":"m6A Profile Dynamics Indicates Regulation of Oyster Development by m6A-RNA Epitranscriptomes","authors":"Lorane Le Franc , Bruno Petton , Pascal Favrel , Guillaume Rivière","doi":"10.1016/j.gpb.2022.12.002","DOIUrl":"10.1016/j.gpb.2022.12.002","url":null,"abstract":"<div><div>The <em>N</em><sup>6</sup>-methylation of RNA adenosines (<em>N</em><sup>6</sup>-methyladenosine, m<sup>6</sup>A) is an important regulator of gene expression with critical implications in vertebrate and insect development. However, the developmental significance of epitranscriptomes in lophotrochozoan organisms remains unknown. Using methylated RNA immunoprecipitation sequencing (MeRIP-seq), we generated transcriptome-wide m<sup>6</sup>A-RNA methylomes covering the entire development of the oyster from oocytes to juveniles. Oyster RNA classes display specific m<sup>6</sup>A signatures, with messenger RNAs (mRNAs) and long non-coding RNAs (lncRNAs) exhibiting distinct profiles and being highly methylated compared to transposable element (TE) transcripts. Epitranscriptomes are dynamic and correspond to the chronological steps of development (cleavage, gastrulation, organogenesis, and <strong>metamorphosis</strong>), with minimal mRNA and lncRNA methylation at the morula stage followed by a global increase. mRNA m<sup>6</sup>A levels are correlated with transcript levels, and shifts in methylation profiles correspond to expression kinetics. Differentially methylated transcripts cluster according to <strong>embryo</strong>-larval stages and bear the corresponding developmental functions (cell division, signal transduction, morphogenesis, and cell differentiation). The m<sup>6</sup>A level of TE transcripts is also regulated and peaks during the gastrulation. We demonstrate that m<sup>6</sup>A-RNA methylomes are dynamic and associated with gene expression regulation during oyster development. The putative epitranscriptome implication in the cleavage, maternal-to-zygotic transition, and cell differentiation in a lophotrochozoan model brings new insights into the control and evolution of developmental processes.</div></div>","PeriodicalId":12528,"journal":{"name":"Genomics, Proteomics & Bioinformatics","volume":"21 4","pages":"Pages 742-755"},"PeriodicalIF":11.5,"publicationDate":"2023-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10787124/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10742751","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 : 2023-08-01DOI: 10.1016/j.gpb.2022.04.004
Ying Lv , Fei Han , Mengxia Liu , Ting Zhang , Guanshen Cui , Jiaojiao Wang , Ying Yang , Yun-Gui Yang , Wenqiang Yang
The unicellular green alga Chlamydomonas reinhardtii (hereafter Chlamydomonas) possesses both plant and animal attributes, and it is an ideal model organism for studying fundamental processes such as photosynthesis, sexual reproduction, and life cycle. N6-methyladenosine (m6A) is the most prevalent mRNA modification, and it plays important roles during sexual reproduction in animals and plants. However, the pattern and function of m6A modification during the sexual reproduction of Chlamydomonas remain unknown. Here, we performed transcriptome and methylated RNA immunoprecipitation sequencing (MeRIP-seq) analyses on six samples from different stages during sexual reproduction of the Chlamydomonas life cycle. The results show that m6A modification frequently occurs at the main motif of DRAC (D = G/A/U, R = A/G) in Chlamydomonas mRNAs. Moreover, m6A peaks in Chlamydomonas mRNAs are mainly enriched in the 3′ untranslated regions (3′UTRs) and negatively correlated with the abundance of transcripts at each stage. In particular, there is a significant negative correlation between the expression levels and the m6A levels of genes involved in the microtubule-associated pathway, indicating that m6A modification influences the sexual reproduction and the life cycle of Chlamydomonas by regulating microtubule-based movement. In summary, our findings are the first to demonstrate the distribution and the functions of m6A modification in Chlamydomonas mRNAs and provide new evolutionary insights into m6A modification in the process of sexual reproduction in other plant organisms.
单细胞绿藻莱茵衣藻(Chlamydomonas reinhardtii，以下简称Chlamydomonas)具有植物和动物的双重属性，是研究光合作用、有性繁殖和生命周期等基本过程的理想模式生物。n6 -甲基腺苷(m6A)是最常见的mRNA修饰，在动植物有性生殖过程中起着重要作用。然而，衣藻有性生殖过程中m6A修饰的模式和功能尚不清楚。在这里，我们对衣藻生命周期有性繁殖不同阶段的6个样本进行了转录组和甲基化RNA免疫沉淀测序(MeRIP-seq)分析。结果表明，在衣藻mrna中，m6A修饰经常发生在DRAC的主基序(D = G/A/U, R = A/G)上。此外，衣藻mrna中的m6A峰主要富集在3′非翻译区(3′UTRs)，且与各阶段转录本丰度呈负相关。特别是微管相关通路相关基因的m6A表达水平与m6A表达水平呈显著负相关，说明m6A修饰通过调节微管为基础的运动影响衣藻的有性生殖和生命周期。综上所述，我们的研究结果首次揭示了m6A修饰在衣藻mrna中的分布和功能，并为其他植物生物有性生殖过程中m6A修饰的进化提供了新的见解。
{"title":"Characteristics of N6-methyladenosine Modification During Sexual Reproduction of Chlamydomonas reinhardtii","authors":"Ying Lv , Fei Han , Mengxia Liu , Ting Zhang , Guanshen Cui , Jiaojiao Wang , Ying Yang , Yun-Gui Yang , Wenqiang Yang","doi":"10.1016/j.gpb.2022.04.004","DOIUrl":"10.1016/j.gpb.2022.04.004","url":null,"abstract":"<div><div>The unicellular green alga <em><strong>Chlamydomonas reinhardtii</strong></em> (hereafter <em>Chlamydomonas</em>) possesses both plant and animal attributes, and it is an ideal model organism for studying fundamental processes such as <strong>photosynthesis</strong>, <strong>sexual reproduction</strong>, and life cycle. <em><strong>N</strong></em><sup><strong>6</strong></sup><strong>-methyladenosine</strong> (m<sup>6</sup>A) is the most prevalent mRNA modification, and it plays important roles during sexual reproduction in animals and plants. However, the pattern and function of m<sup>6</sup>A modification during the sexual reproduction of <em>Chlamydomonas</em> remain unknown. Here, we performed transcriptome and methylated RNA immunoprecipitation sequencing (MeRIP-seq) analyses on six samples from different stages during sexual reproduction of the <em>Chlamydomonas</em> life cycle<em>.</em> The results show that m<sup>6</sup>A modification frequently occurs at the main motif of DRAC (D = G/A/U, R = A/G) in <em>Chlamydomonas</em> mRNAs. Moreover, m<sup>6</sup>A peaks in <em>Chlamydomonas</em> mRNAs are mainly enriched in the 3′ untranslated regions (3′UTRs) and negatively correlated with the abundance of transcripts at each stage. In particular, there is a significant negative correlation between the expression levels and the m<sup>6</sup>A levels of genes involved in the <strong>microtubule-associated pathway</strong>, indicating that m<sup>6</sup>A modification influences the sexual reproduction and the life cycle of <em>Chlamydomonas</em> by regulating microtubule-based movement. In summary, our findings are the first to demonstrate the distribution and the functions of m<sup>6</sup>A modification in <em>Chlamydomonas</em> mRNAs and provide new evolutionary insights into m<sup>6</sup>A modification in the process of sexual reproduction in other plant organisms.</div></div>","PeriodicalId":12528,"journal":{"name":"Genomics, Proteomics & Bioinformatics","volume":"21 4","pages":"Pages 756-768"},"PeriodicalIF":11.5,"publicationDate":"2023-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10787120/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138453356","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 : 2023-06-01DOI: 10.1016/j.gpb.2022.12.010
Sijia Wu , Zhiwei Fan , Pora Kim , Liyu Huang , Xiaobo Zhou
Adenosine-to-inosine (A-to-I) RNA editing, constituting nearly 90% of all RNA editing events in humans, has been reported to contribute to the tumorigenesis in diverse cancers. However, the comprehensive map for functional A-to-I RNA editing events in cancers is still insufficient. To fill this gap, we systematically and intensively analyzed multiple tumorigenic mechanisms of A-to-I RNA editing events in samples across 33 cancer types from The Cancer Genome Atlas. For individual candidate among ∼ 1,500,000 quantified RNA editing events, we performed diverse types of downstream functional annotations. Finally, we identified 24,236 potentially functional A-to-I RNA editing events, including the cases in APOL1, IGFBP3, GRIA2, BLCAP, and miR-589-3p. These events might play crucial roles in the scenarios of tumorigenesis, due to their tumor-related editing frequencies or probable effects on altered expression profiles, protein functions, splicing patterns, and microRNA regulations of tumor genes. Our functional A-to-I RNA editing events (https://ccsm.uth.edu/CAeditome/) will help better understand the cancer pathology from the A-to-I RNA editing aspect.
{"title":"The Integrative Studies on the Functional A-to-I RNA Editing Events in Human Cancers","authors":"Sijia Wu , Zhiwei Fan , Pora Kim , Liyu Huang , Xiaobo Zhou","doi":"10.1016/j.gpb.2022.12.010","DOIUrl":"10.1016/j.gpb.2022.12.010","url":null,"abstract":"<div><div>Adenosine-to-inosine (A-to-I) RNA editing, constituting nearly 90% of all RNA editing events in humans, has been reported to contribute to the tumorigenesis in diverse <strong>cancers</strong>. However, the comprehensive map for functional <strong>A-to-I RNA editing</strong> events in cancers is still insufficient. To fill this gap, we systematically and intensively analyzed multiple tumorigenic mechanisms of A-to-I RNA editing events in samples across 33 cancer types from The Cancer Genome Atlas. For individual candidate among ∼ 1,500,000 quantified RNA editing events, we performed diverse types of downstream functional annotations. Finally, we identified 24,236 potentially functional A-to-I RNA editing events, including the cases in <em>APOL1</em>, <em>IGFBP3</em>, <em>GRIA2</em>, <em>BLCAP</em>, and miR-589-3p. These events might play crucial roles in the scenarios of tumorigenesis, due to their tumor-related editing frequencies or probable effects on altered expression profiles, protein functions, splicing patterns, and microRNA regulations of tumor genes. Our functional A-to-I RNA editing events (<span><span>https://ccsm.uth.edu/CAeditome/</span><svg><path></path></svg></span>) will help better understand the cancer pathology from the A-to-I RNA editing aspect.</div></div>","PeriodicalId":12528,"journal":{"name":"Genomics, Proteomics & Bioinformatics","volume":"21 3","pages":"Pages 619-631"},"PeriodicalIF":11.5,"publicationDate":"2023-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10787018/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9304024","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 : 2023-06-01DOI: 10.1016/j.gpb.2022.09.008
Sébastien Leblanc , Marie A. Brunet , Jean-François Jacques , Amina M. Lekehal , Andréa Duclos , Alexia Tremblay , Alexis Bruggeman-Gascon , Sondos Samandi , Mylène Brunelle , Alan A. Cohen , Michelle S. Scott , Xavier Roucou
Recent proteogenomic approaches have led to the discovery that regions of the transcriptome previously annotated as non-coding regions [i.e., untranslated regions (UTRs), open reading frames overlapping annotated coding sequences in a different reading frame, and non-coding RNAs] frequently encode proteins, termed alternative proteins (altProts). This suggests that previously identified protein–protein interaction (PPI) networks are partially incomplete because altProts are not present in conventional protein databases. Here, we used the proteogenomic resource OpenProt and a combined spectrum- and peptide-centric analysis for the re-analysis of a high-throughput human network proteomics dataset, thereby revealing the presence of 261 altProts in the network. We found 19 genes encoding both an annotated (reference) and an alternative protein interacting with each other. Of the 117 altProts encoded by pseudogenes, 38 are direct interactors of reference proteins encoded by their respective parental genes. Finally, we experimentally validate several interactions involving altProts. These data improve the blueprints of the human PPI network and suggest functional roles for hundreds of altProts.
{"title":"Newfound Coding Potential of Transcripts Unveils Missing Members of Human Protein Communities","authors":"Sébastien Leblanc , Marie A. Brunet , Jean-François Jacques , Amina M. Lekehal , Andréa Duclos , Alexia Tremblay , Alexis Bruggeman-Gascon , Sondos Samandi , Mylène Brunelle , Alan A. Cohen , Michelle S. Scott , Xavier Roucou","doi":"10.1016/j.gpb.2022.09.008","DOIUrl":"10.1016/j.gpb.2022.09.008","url":null,"abstract":"<div><div>Recent proteogenomic approaches have led to the discovery that regions of the transcriptome previously annotated as non-coding regions [<em>i.e.</em>, untranslated regions (UTRs), open reading frames overlapping annotated coding sequences in a different reading frame, and non-coding RNAs] frequently encode proteins, termed <strong>alternative proteins</strong> (<strong>altProts</strong>). This suggests that previously identified protein–protein interaction (PPI) networks are partially incomplete because altProts are not present in conventional protein databases. Here, we used the proteogenomic resource OpenProt and a combined spectrum- and peptide-centric analysis for the re-analysis of a high-throughput human network proteomics dataset, thereby revealing the presence of 261 altProts in the network. We found 19 genes encoding both an annotated (reference) and an alternative protein interacting with each other. Of the 117 altProts encoded by <strong>pseudogenes</strong>, 38 are direct interactors of reference proteins encoded by their respective parental genes. Finally, we experimentally validate several interactions involving altProts. These data improve the blueprints of the human PPI network and suggest functional roles for hundreds of altProts.</div></div>","PeriodicalId":12528,"journal":{"name":"Genomics, Proteomics & Bioinformatics","volume":"21 3","pages":"Pages 515-534"},"PeriodicalIF":11.5,"publicationDate":"2023-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10787177/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"40389052","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 : 2023-06-01DOI: 10.1016/j.gpb.2022.11.007
Xiangyu Pan , Zhaoxia Ma , Xinqi Sun , Hui Li , Tingting Zhang , Chen Zhao , Nini Wang , Rasmus Heller , Wing Hung Wong , Wen Wang , Yu Jiang , Yong Wang
The genetic information coded in DNA leads to trait innovation via a gene regulatory network (GRN) in development. Here, we developed a conserved non-coding element interpretation method to integrate multi-omics data into gene regulatory network (CNEReg) to investigate the ruminant multi-chambered stomach innovation. We generated paired expression and chromatin accessibility data during rumen and esophagus development in sheep, and revealed 1601 active ruminant-specific conserved non-coding elements (active-RSCNEs). To interpret the function of these active-RSCNEs, we defined toolkit transcription factors (TTFs) and modeled their regulation on rumen-specific genes via batteries of active-RSCNEs during development. Our developmental GRN revealed 18 TTFs and 313 active-RSCNEs regulating 7 rumen functional modules. Notably, 6 TTFs (OTX1, SOX21, HOXC8, SOX2, TP63, and PPARG), as well as 16 active-RSCNEs, functionally distinguished the rumen from the esophagus. Our study provides a systematic approach to understanding how gene regulation evolves and shapes complex traits by putting evo-devo concepts into practice with developmental multi-omics data.
{"title":"CNEReg Interprets Ruminant-specific Conserved Non-coding Elements by Developmental Gene Regulatory Network","authors":"Xiangyu Pan , Zhaoxia Ma , Xinqi Sun , Hui Li , Tingting Zhang , Chen Zhao , Nini Wang , Rasmus Heller , Wing Hung Wong , Wen Wang , Yu Jiang , Yong Wang","doi":"10.1016/j.gpb.2022.11.007","DOIUrl":"10.1016/j.gpb.2022.11.007","url":null,"abstract":"<div><div>The genetic information coded in DNA leads to <strong>trait innovation</strong> via a <strong>gene regulatory network</strong> (GRN) in development. Here, we developed a <strong>conserved non-coding element</strong> interpretation method to integrate multi-omics data into gene r<u>eg</u>ulatory network (CNEReg) to investigate the <strong>ruminant</strong> multi-chambered stomach innovation. We generated paired expression and chromatin accessibility data during rumen and esophagus development in sheep, and revealed 1601 active ruminant-specific conserved non-coding elements (active-RSCNEs). To interpret the function of these active-RSCNEs, we defined <strong>toolkit transcription factors</strong> (TTFs) and modeled their regulation on rumen-specific genes via batteries of active-RSCNEs during development. Our developmental GRN revealed 18 TTFs and 313 active-RSCNEs regulating 7 rumen functional modules. Notably, 6 TTFs (OTX1, SOX21, HOXC8, SOX2, TP63, and PPARG), as well as 16 active-RSCNEs, functionally distinguished the rumen from the esophagus. Our study provides a systematic approach to understanding how gene regulation evolves and shapes complex traits by putting evo-devo concepts into practice with developmental multi-omics data.</div></div>","PeriodicalId":12528,"journal":{"name":"Genomics, Proteomics & Bioinformatics","volume":"21 3","pages":"Pages 632-648"},"PeriodicalIF":11.5,"publicationDate":"2023-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10787174/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10365071","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 : 2023-06-01DOI: 10.1016/j.gpb.2023.08.002
Guobin Chang , Xiaoya Yuan , Qixin Guo , Hao Bai , Xiaofang Cao , Meng Liu , Zhixiu Wang , Bichun Li , Shasha Wang , Yong Jiang , Zhiquan Wang , Yang Zhang , Qi Xu , Qianqian Song , Rui Pan , Lingling Qiu , Tiantian Gu , Xinsheng Wu , Yulin Bi , Zhengfeng Cao , Guohong Chen
The Chinese crested (CC) duck is a unique indigenous waterfowl breed, which has a crest cushion that affects its survival rate. Therefore, the CC duck is an ideal model to investigate the genetic compensation response to maintain genetic stability. In the present study, we first generated a chromosome-level genome of CC ducks. Comparative genomics revealed that genes related to tissue repair, immune function, and tumors were under strong positive selection, indicating that these adaptive changes might enhance cancer resistance and immune response to maintain the genetic stability of CC ducks. We also assembled a Chinese spot-billed (Csp-b) duck genome, and detected the structural variations (SVs) in the genome assemblies of three ducks (i.e., CC duck, Csp-b duck, and Peking duck). Functional analysis revealed that several SVs were related to the immune system of CC ducks, further strongly suggesting that genetic compensation in the anti-tumor and immune systems supports the survival of CC ducks. Moreover, we confirmed that the CC duck originated from the mallard ducks. Finally, we revealed the physiological and genetic basis of crest traits and identified a causative mutation in TAS2R40 that leads to crest formation. Overall, the findings of this study provide new insights into the role of genetic compensation in adaptive evolution.
{"title":"The First Crested Duck Genome Reveals Clues to Genetic Compensation and Crest Cushion Formation","authors":"Guobin Chang , Xiaoya Yuan , Qixin Guo , Hao Bai , Xiaofang Cao , Meng Liu , Zhixiu Wang , Bichun Li , Shasha Wang , Yong Jiang , Zhiquan Wang , Yang Zhang , Qi Xu , Qianqian Song , Rui Pan , Lingling Qiu , Tiantian Gu , Xinsheng Wu , Yulin Bi , Zhengfeng Cao , Guohong Chen","doi":"10.1016/j.gpb.2023.08.002","DOIUrl":"10.1016/j.gpb.2023.08.002","url":null,"abstract":"<div><div>The <strong>Chinese crested (CC) duck</strong> is a unique indigenous waterfowl breed, which has a <strong>crest cushion</strong> that affects its survival rate. Therefore, the CC duck is an ideal model to investigate the <strong>genetic compensation</strong> response to maintain genetic stability. In the present study, we first generated a chromosome-level genome of CC ducks. Comparative genomics revealed that genes related to tissue repair, immune function, and tumors were under strong positive selection, indicating that these adaptive changes might enhance cancer resistance and immune response to maintain the genetic stability of CC ducks. We also assembled a Chinese spot-billed (Csp-b) duck genome, and detected the structural variations (SVs) in the <strong>genome assembl</strong><strong>ies</strong> of three ducks (<em>i.e.</em>, CC duck, Csp-b duck, and Peking duck). Functional analysis revealed that several SVs were related to the immune system of CC ducks, further strongly suggesting that genetic compensation in the anti-tumor and immune systems supports the survival of CC ducks. Moreover, we confirmed that the CC duck originated from the mallard ducks. Finally, we revealed the physiological and genetic basis of crest traits and identified a causative mutation in <em>TAS2R40</em> that leads to crest formation. Overall, the findings of this study provide new insights into the role of genetic compensation in adaptive evolution.</div></div>","PeriodicalId":12528,"journal":{"name":"Genomics, Proteomics & Bioinformatics","volume":"21 3","pages":"Pages 483-500"},"PeriodicalIF":11.5,"publicationDate":"2023-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10787023/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10126085","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 : 2023-06-01DOI: 10.1016/j.gpb.2023.01.003
Guoli Ji , Qi Tang , Sheng Zhu , Junyi Zhu , Pengchao Ye , Shuting Xia , Xiaohui Wu
Alternative polyadenylation (APA) contributes to transcriptome complexity and gene expression regulation and has been implicated in various cellular processes and diseases. Single-cell RNA sequencing (scRNA-seq) has enabled the profiling of APA at the single-cell level; however, the spatial information of cells is not preserved in scRNA-seq. Alternatively, spatial transcriptomics (ST) technologies provide opportunities to decipher the spatial context of the transcriptomic landscape. Pioneering studies have revealed potential spatially variable genes and/or splice isoforms; however, the pattern of APA usage in spatial contexts remains unappreciated. In this study, we developed a toolkit called stAPAminer for mining spatial patterns of APA from spatially barcoded ST data. APA sites were identified and quantified from the ST data. In particular, an imputation model based on the k-nearest neighbors algorithm was designed to recover APA signals, and then APA genes with spatial patterns of APA usage variation were identified. By analyzing well-established ST data of the mouse olfactory bulb (MOB), we presented a detailed view of spatial APA usage across morphological layers of the MOB. We compiled a comprehensive list of genes with spatial APA dynamics and obtained several major spatial expression patterns that represent spatial APA dynamics in different morphological layers. By extending this analysis to two additional replicates of the MOB ST data, we observed that the spatial APA patterns of several genes were reproducible among replicates. stAPAminer employs the power of ST to explore the transcriptional atlas of spatial APA patterns with spatial resolution. This toolkit is available at https://github.com/BMILAB/stAPAminer and https://ngdc.cncb.ac.cn/biocode/tools/BT007320.
{"title":"stAPAminer: Mining Spatial Patterns of Alternative Polyadenylation for Spatially Resolved Transcriptomic Studies","authors":"Guoli Ji , Qi Tang , Sheng Zhu , Junyi Zhu , Pengchao Ye , Shuting Xia , Xiaohui Wu","doi":"10.1016/j.gpb.2023.01.003","DOIUrl":"10.1016/j.gpb.2023.01.003","url":null,"abstract":"<div><div><strong>Alternative polyadenylation</strong> (APA) contributes to transcriptome complexity and gene expression regulation and has been implicated in various cellular processes and diseases. <strong>Single-cell RNA sequencing</strong> (scRNA-seq) has enabled the profiling of APA at the single-cell level; however, the spatial information of cells is not preserved in scRNA-seq. Alternatively, <strong>spatial transcriptomics</strong> (ST) technologies provide opportunities to decipher the spatial context of the transcriptomic landscape. Pioneering studies have revealed potential spatially variable genes and/or splice isoforms; however, the pattern of APA usage in spatial contexts remains unappreciated. In this study, we developed a toolkit called stAPAminer for mining <strong>spatial patterns</strong> of APA from spatially barcoded ST data. APA sites were identified and quantified from the ST data. In particular, an <strong>imputation</strong> model based on the k-nearest neighbors algorithm was designed to recover APA signals, and then APA genes with spatial patterns of APA usage variation were identified. By analyzing well-established ST data of the mouse olfactory bulb (MOB), we presented a detailed view of spatial APA usage across morphological layers of the MOB. We compiled a comprehensive list of genes with spatial APA dynamics and obtained several major spatial expression patterns that represent spatial APA dynamics in different morphological layers. By extending this analysis to two additional replicates of the MOB ST data, we observed that the spatial APA patterns of several genes were reproducible among replicates. stAPAminer employs the power of ST to explore the transcriptional atlas of spatial APA patterns with spatial resolution. This toolkit is available at <span><span>https://github.com/BMILAB/stAPAminer</span><svg><path></path></svg></span> and <span><span>https://ngdc.cncb.ac.cn/biocode/tools/BT007320</span><svg><path></path></svg></span>.</div></div>","PeriodicalId":12528,"journal":{"name":"Genomics, Proteomics & Bioinformatics","volume":"21 3","pages":"Pages 601-618"},"PeriodicalIF":11.5,"publicationDate":"2023-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10787175/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9117826","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}
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