Genomics, Proteomics & Bioinformatics最新文献_第6页

Identifying RNA Modifications by Direct RNA Sequencing Reveals Complexity of Epitranscriptomic Dynamics in Rice 通过直接RNA测序鉴定RNA修饰揭示水稻表观转录组动力学的复杂性。

IF 11.5 2区生物学 Q1 GENETICS & HEREDITY

Genomics, Proteomics & Bioinformatics

Pub Date : 2023-08-01 DOI: 10.1016/j.gpb.2023.02.002

Feng Yu, Huanhuan Qi, Li Gao, Sen Luo, Rebecca Njeri Damaris, Yinggen Ke, Wenhua Wu, Pingfang Yang

Transcriptome analysis based on high-throughput sequencing of a cDNA library has been widely applied to functional genomic studies. However, the cDNA dependence of most RNA sequencing techniques constrains their ability to detect base modifications on RNA, which is an important element for the post-transcriptional regulation of gene expression. To comprehensively profile the N⁶-methyladenosine (m⁶A) and N⁵-methylcytosine (m⁵C) modifications on RNA, direct RNA sequencing (DRS) using the latest Oxford Nanopore Technology was applied to analyze the transcriptome of six tissues in rice. Approximately 94 million reads were generated, with an average length ranging from 619 nt to 1013 nt, and a total of 45,707 transcripts across 34,763 genes were detected. Expression profiles of transcripts at the isoform level were quantified among tissues. Transcriptome-wide mapping of m⁶A and m⁵C demonstrated that both modifications exhibited tissue-specific characteristics. The transcripts with m⁶A modifications tended to be modified by m⁵C, and the transcripts with modifications presented higher expression levels along with shorter poly(A) tails than transcripts without modifications, suggesting the complexity of gene expression regulation. Gene Ontology analysis demonstrated that m⁶A- and m⁵C-modified transcripts were involved in central metabolic pathways related to the life cycle, with modifications on the target genes selected in a tissue-specific manner. Furthermore, most modified sites were located within quantitative trait loci that control important agronomic traits, highlighting the value of cloning functional loci. The results provide new insights into the expression regulation complexity and data resource of the transcriptome and epitranscriptome, improving our understanding of the rice genome.

基于cDNA文库高通量测序的转录组分析已广泛应用于功能基因组研究。然而，大多数RNA测序技术对cDNA的依赖限制了它们检测RNA上的碱基修饰的能力，而RNA修饰是基因转录后调控的重要元素。为了全面分析n6 -甲基腺苷(m6A)和n5 -甲基胞嘧啶(m5C)在RNA上的修饰，采用最新的牛津纳米孔技术(Oxford Nanopore Technology)对水稻6个组织的转录组进行了直接RNA测序(DRS)分析。共生成了约9400万个reads，平均长度为619 ~ 1013 nt，共检测到34,763个基因的45707个转录本。在同工型水平上定量组织间转录本的表达谱。m6A和m5C的转录组图谱显示，这两种修饰都具有组织特异性。m6A修饰的转录本更容易被m5C修饰，修饰后的转录本比未修饰的转录本表达量更高，多A尾更短，表明基因表达调控的复杂性。基因本体分析表明，m6A和m5c修饰的转录本参与了与生命周期相关的中枢代谢途径，并以组织特异性的方式选择了靶基因的修饰。此外，大多数修饰位点位于控制重要农艺性状的数量性状位点内，这突出了克隆功能位点的价值。研究结果对水稻转录组和表转录组的表达调控复杂性和数据来源提供了新的认识，提高了我们对水稻基因组的认识。

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引用次数: 0

Multi-omics of Circular RNAs and Their Responses to Hormones in Moso Bamboo (Phyllostachys edulis) 毛竹环状rna的多组学研究及其对激素的响应。

IF 11.5 2区生物学 Q1 GENETICS & HEREDITY

Genomics, Proteomics & Bioinformatics

Pub Date : 2023-08-01 DOI: 10.1016/j.gpb.2023.01.007

Yongsheng Wang , Huihui Wang , Huiyuan Wang , Ruifan Zhou , Ji Wu , Zekun Zhang , Yandong Jin , Tao Li , Markus V. Kohnen , Xuqing Liu , Wentao Wei , Kai Chen , Yubang Gao , Jiazhi Ding , Hangxiao Zhang , Bo Liu , Chentao Lin , Lianfeng Gu

Circular RNAs (circRNAs) are endogenous non-coding RNAs with covalently closed structures, which have important functions in plants. However, their biogenesis, degradation, and function upon treatment with gibberellins (GAs) and auxins (1-naphthaleneacetic acid, NAA) remain unknown. Here, we systematically identified and characterized the expression patterns, evolutionary conservation, genomic features, and internal structures of circRNAs using RNase R-treated libraries from moso bamboo (Phyllostachys edulis) seedlings. Moreover, we investigated the biogenesis of circRNAs dependent on both cis- and trans-regulation. We explored the function of circRNAs, including their roles in regulating microRNA (miRNA)-related genes and modulating the alternative splicing of their linear counterparts. Importantly, we developed a customized degradome sequencing approach to detect miRNA-mediated cleavage of circRNAs. Finally, we presented a comprehensive view of the participation of circRNAs in the regulation of hormone metabolism upon treatment of bamboo seedlings with GA and NAA. Collectively, our study provides insights into the biogenesis, function, and miRNA-mediated degradation of circRNAs in moso bamboo.

环状rna (circRNAs)是一种具有共价封闭结构的内源性非编码rna，在植物中具有重要的功能。然而，它们的生物发生、降解和在赤霉素(GAs)和生长素(1-萘乙酸，NAA)处理下的功能仍然未知。本研究利用RNase r处理的毛竹幼苗文库，系统地鉴定和表征了环状rna的表达模式、进化保守性、基因组特征和内部结构。此外，我们还研究了依赖于顺式和反式调控的环状rna的生物发生。我们探索了环状rna的功能，包括它们在调节microRNA (miRNA)相关基因和调节其线性对应物的选择性剪接中的作用。重要的是，我们开发了一种定制的降解组测序方法来检测mirna介导的环状rna切割。最后，我们全面介绍了在GA和NAA处理竹幼苗后，circrna参与调节激素代谢的情况。总的来说，我们的研究深入了解了毛竹中环状rna的生物发生、功能和mirna介导的降解。

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引用次数: 0

Transcriptome-wide Dynamics of m6A mRNA Methylation During Porcine Spermatogenesis 猪精子发生过程中 m6A mRNA 甲基化在整个转录组的动态变化

IF 11.5 2区生物学 Q1 GENETICS & HEREDITY

Genomics, Proteomics & Bioinformatics

Pub Date : 2023-08-01 DOI: 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.

精子发生是睾丸中发生的一个持续过程，在这个过程中，二倍体精原干细胞（SSC）分化并生成单倍体精子。这一高效而复杂的过程在多个层面上进行协调。N6-甲基腺苷（m6A）是mRNA中普遍存在的一种表观遗传修饰，与精子发生过程中的转录调控有关。然而，m6A修饰在非啮齿类哺乳动物物种中的动态变化仍不清楚。在这里，我们系统地研究了猪精子发生过程中m6A的概况和作用。通过分析 m6A 在精原细胞、精母细胞和圆形精子中的转录组分布，我们发现了猪和鼠具有生精功能的基因之间全球保守的 m6A 模式。我们发现，m6A 富集在一组专门编码代谢酶和调节因子的基因中。此外，猪雄性生殖细胞的转录组也可能受到 m6A 的修饰。我们的数据表明，m6A 在猪的精子发生过程中起着调控作用，这与小鼠的情况类似。三个基因（SETDB1、FOXO1 和 FOXO3）对决定造精细胞的命运至关重要，它们就是这方面的例证。据我们所知，这项研究首次揭示了m6A在大型动物精子发生过程中的表达谱和作用，为我们深入了解非啮齿类哺乳动物物种中雄性终生生育能力背后错综复杂的转录调控提供了线索。

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引用次数: 0

m6A-TSHub: Unveiling the Context-specific m6A Methylation and m6A-affecting Mutations in 23 Human Tissues m6A- tshub:揭示23种人体组织中特定环境的m6A甲基化和m6A影响突变。

IF 11.5 2区生物学 Q1 GENETICS & HEREDITY

Genomics, Proteomics & Bioinformatics

Pub Date : 2023-08-01 DOI: 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.

作为mRNA和lncRNA上最普遍存在的表观遗传标记，n6 -甲基腺苷(m6A) RNA甲基化已被证明参与必要的生物过程。最近的研究揭示了m6A甲基化在人体组织中的独特模式，阐明m6A甲基化的组织特异性存在和通路仍然是一个主要的挑战。我们在这里提出了一个综合的在线平台m6A- tshub，用于揭示可能调节m6A表观遗传标记的上下文特异性m6A甲基化和基因突变。m6A- tshub由四个核心组件组成，包括:(1)m6A- tsdb，这是一个综合数据库，分别包含来自23个人体组织的184,554个功能性注释的m6A位点和来自25种肿瘤的499,369个m6A位点;(2) m6A- tsfinder，基于多实例深度神经网络构建的基于RNA序列的m6A甲基化位点高精度预测web服务器;(3) m6A- tsvar，一个用于评估遗传变异对组织特异性m6A RNA修饰影响的web服务器;(4) m6A- cavar，一个包含587,983个癌症基因组图谱(TCGA)癌症突变(来自27种癌症类型)的数据库，这些突变被预测会影响癌症原发组织中的m6A修饰。该数据库将为研究特定组织(或癌症类型)的m6A甲基组和表转录组紊乱的遗传因素提供有用的资源。m6A-TSHub可访问www.xjtlu.edu.cn/biologicalsciences/m6ats。

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引用次数: 0

N6-methyladenosine and Its Implications in Viruses n6 -甲基腺苷及其在病毒中的意义。

IF 11.5 2区生物学 Q1 GENETICS & HEREDITY

Genomics, Proteomics & Bioinformatics

Pub Date : 2023-08-01 DOI: 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.

n6 -甲基腺嘌呤(N6-methyladenine, m6A)是哺乳动物信使RNA (mRNA)中最丰富的RNA修饰，参与和调控许多重要的生物活动，如组织发育和干细胞分化。由于对m6A认识的提高，研究人员发现m6A的生物学功能可以与mRNA代谢的许多阶段相关联，并且m6A可以调节多种复杂的生物学过程。除了在哺乳动物mrna上的位置外，m6A还在病毒转录本上被鉴定出来。m6A还在许多病毒的生命周期和病毒在宿主细胞中的复制中发挥重要作用。本文就m6A的检测方法、m6A相关蛋白及m6A的功能作一综述。我们还总结了m6a相关蛋白在病毒复制和感染中的作用。我们希望这一综述能够为研究人员阐明与病毒相关的表转录组的复杂机制提供一些见解，并为进一步研究其他修饰的核碱基作用于病毒复制等过程的机制提供信息。我们也期待这篇综述能够激发化学、生物学和医学等不同领域的合作研究，促进抗病毒药物和疫苗的开发。

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引用次数: 0

Specific Regulation of m6A by SRSF7 Promotes the Progression of Glioblastoma SRSF7对m6A的特异性调控促进了胶质母细胞瘤的进展

IF 11.5 2区生物学 Q1 GENETICS & HEREDITY

Genomics, Proteomics & Bioinformatics

Pub Date : 2023-08-01 DOI: 10.1016/j.gpb.2021.11.001

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 , Jun Li

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).

丝氨酸/精氨酸丰富的剪接因子7（SRSF7）是一种已知的剪接因子，已被发现在多种癌症中发挥致癌作用。然而，其致癌作用的机制尚未得到很好的研究。在这里，基于对不同细胞系的 N6-甲基腺苷（m6A）共甲基化网络分析，我们发现 SRSF7 的基因表达与胶质母细胞瘤（GBM）细胞特异性 m6A 甲基化呈正相关。我们随后指出，SRSF7 是一种新型 m6A 调节因子，它通过招募甲基转移酶复合物，特异性地促进其结合位点附近参与细胞增殖和迁移的 mRNA 上的 m6A 甲基化。此外，SRSF7 促进 GBM 细胞的增殖和迁移主要依赖于 m6A 甲基转移酶的存在。PDZ结合激酶（PBK）mRNA上的两个m6A位点受SRSF7调控，并通过胰岛素样生长因子2 mRNA结合蛋白2（IGF2BP2）的识别，部分介导SRSF7在GBM细胞中的作用。总之，我们的发现揭示了 SRSF7 在调控 m6A 中的新作用，并验证了 RNA 结合蛋白（RBPs）介导的 m6A 时空特异性调控的存在及其功能重要性。

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引用次数: 0

RNA Structural Dynamics Modulate EGFR-TKI Resistance Through Controlling YRDC Translation in NSCLC Cells RNA结构动力学通过控制YRDC在NSCLC细胞中的翻译调节EGFR-TKI耐药性。

IF 11.5 2区生物学 Q1 GENETICS & HEREDITY

Genomics, Proteomics & Bioinformatics

Pub Date : 2023-08-01 DOI: 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。

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引用次数: 0

Screening Linear and Circular RNA Transcripts from Stress Granules 从应激颗粒中筛选线性和环状 RNA 转录本

IF 11.5 2区生物学 Q1 GENETICS & HEREDITY

Genomics, Proteomics & Bioinformatics

Pub Date : 2023-08-01 DOI: 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.

应激颗粒（SGs）是在应激条件下形成的细胞质核糖核蛋白集合体，与各种生物过程和人类疾病有关。之前的研究已经报道了一些蛋白质和线性 RNA 在 SG 组装中的调控作用。然而，尚未发现环状 RNA（circRNA）与 SG 之间的关系。在这里，我们利用改进的哺乳动物细胞纯化的SG核心总RNA测序技术筛选了SG中的线性RNA和环状RNA，发现了特异性定位在SG中的环状转录本。此外，一些SG富集的circRNA在肝细胞癌（HCC）和邻近组织中的表达存在差异。这些结果表明了 circRNAs 在 SG 形成过程中的调控作用，并为深入了解 circRNAs 和 SGs 在 HCC 中的生物学功能提供了思路。

引用次数: 0

Dynamic Landscapes of tRNA Transcriptomes and Translatomes in Diverse Mouse Tissues 不同小鼠组织中tRNA转录组和翻译组的动态景观。

IF 11.5 2区生物学 Q1 GENETICS & HEREDITY

Genomics, Proteomics & Bioinformatics

Pub Date : 2023-08-01 DOI: 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.

尽管tRNA在翻译过程中的功能已经得到了很好的证实，但在哺乳动物中，tRNA丰度是否与翻译效率(TE)密切相关仍存在争议。此外，在哺乳动物中，trna的表达对组织特异性蛋白质组的建立有多重要，还没有得到很好的解决。在这里，我们使用去甲基化酶-tRNA测序(DM-tRNA-seq)测量了小鼠大脑、心脏和睾丸中的tRNA表达，使用核糖体标记测序(RiboTag-seq)测量了mrna的TE。在不同组织中观察到tRNA同位解码器的表达有显著差异。当通过排列反密码子来考虑异位解码器分组对减少变异的统计效应时，我们观察到所有样本中反密码子表达变异的预期减少，反密码子使用偏差的预期较小，以及氨基酸水平上tRNA同型表达的预期较大。不管它们是否共享相同的反密码子，编码相同氨基酸的同工解码器在不同组织中共同表达。基于tRNA的表达和mrna的TE，我们发现tRNA适应指数(tAI)和TE在同一组织内显著相关，而在组织间不显著;tRNA表达量与翻译肽氨基酸组成在同一组织内呈显著正相关，而在不同组织间无显著正相关。因此，我们假设trna的组织特异性表达可能是由于转录后机制。该研究为tRNA和翻译研究提供了资源，并为tRNA的动力学及其在翻译调控中的作用提供了新的见解。

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引用次数: 0

RNA Modifications and Epitranscriptomics RNA修饰和上皮转录组学。

IF 11.5 2区生物学 Q1 GENETICS & HEREDITY

Genomics, Proteomics & Bioinformatics

Pub Date : 2023-08-01 DOI: 10.1016/j.gpb.2023.10.002

Chengqi Yi , Jianhua Yang

引用次数: 0