Pub Date : 2024-07-12DOI: 10.1038/s41576-024-00763-5
Henry Ertl
Two studies in Nature reveal the mechanistic and structural properties of a family of mobile genetic elements that can be reprogrammed to engineer genome modifications.
{"title":"Programmable DNA rearrangements using bridge RNAs","authors":"Henry Ertl","doi":"10.1038/s41576-024-00763-5","DOIUrl":"10.1038/s41576-024-00763-5","url":null,"abstract":"Two studies in Nature reveal the mechanistic and structural properties of a family of mobile genetic elements that can be reprogrammed to engineer genome modifications.","PeriodicalId":19067,"journal":{"name":"Nature Reviews Genetics","volume":"25 9","pages":"599-599"},"PeriodicalIF":39.1,"publicationDate":"2024-07-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141597639","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-07-09DOI: 10.1038/s41576-024-00749-3
Joy S. Xiang, Danielle M. Schafer, Katherine L. Rothamel, Gene W. Yeo
Protein–RNA interactions are central to all RNA processing events, with pivotal roles in the regulation of gene expression and cellular functions. Dysregulation of these interactions has been increasingly linked to the pathogenesis of human diseases. High-throughput approaches to identify RNA-binding proteins and their binding sites on RNA — in particular, ultraviolet crosslinking followed by immunoprecipitation (CLIP) — have helped to map the RNA interactome, yielding transcriptome-wide protein–RNA atlases that have contributed to key mechanistic insights into gene expression and gene-regulatory networks. Here, we review these recent advances, explore the effects of cellular context on RNA binding, and discuss how these insights are shaping our understanding of cellular biology. We also review the potential therapeutic applications arising from new knowledge of protein–RNA interactions. RNA-binding proteins regulate the lifecycle of RNA, and their dysregulation is associated with diseases such as cancer and neurodegeneration. Using methods based on ultraviolet crosslinking followed by immunoprecipitation (CLIP), we can now begin to decode the mechanisms of the interactions between RNA-binding proteins and RNA. This Review discusses recent insights from and future applications of these methodologies.
{"title":"Decoding protein–RNA interactions using CLIP-based methodologies","authors":"Joy S. Xiang, Danielle M. Schafer, Katherine L. Rothamel, Gene W. Yeo","doi":"10.1038/s41576-024-00749-3","DOIUrl":"10.1038/s41576-024-00749-3","url":null,"abstract":"Protein–RNA interactions are central to all RNA processing events, with pivotal roles in the regulation of gene expression and cellular functions. Dysregulation of these interactions has been increasingly linked to the pathogenesis of human diseases. High-throughput approaches to identify RNA-binding proteins and their binding sites on RNA — in particular, ultraviolet crosslinking followed by immunoprecipitation (CLIP) — have helped to map the RNA interactome, yielding transcriptome-wide protein–RNA atlases that have contributed to key mechanistic insights into gene expression and gene-regulatory networks. Here, we review these recent advances, explore the effects of cellular context on RNA binding, and discuss how these insights are shaping our understanding of cellular biology. We also review the potential therapeutic applications arising from new knowledge of protein–RNA interactions. RNA-binding proteins regulate the lifecycle of RNA, and their dysregulation is associated with diseases such as cancer and neurodegeneration. Using methods based on ultraviolet crosslinking followed by immunoprecipitation (CLIP), we can now begin to decode the mechanisms of the interactions between RNA-binding proteins and RNA. This Review discusses recent insights from and future applications of these methodologies.","PeriodicalId":19067,"journal":{"name":"Nature Reviews Genetics","volume":"25 12","pages":"879-895"},"PeriodicalIF":39.1,"publicationDate":"2024-07-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141561351","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-07-05DOI: 10.1038/s41576-024-00758-2
Andrey Tvardovskiy, Saulius Lukauskas
In this Tools of the Trade article, Andrey Tvardovskiy and Saulius Lukauskas introduce the web resource MARCS, which offers a set of visualization tools to explore chromatin regulatory circuits from either a protein- or modification-centred perspective.
在这篇 "贸易工具 "文章中，Andrey Tvardovskiy 和 Saulius Lukauskas 介绍了 MARCS 网络资源，它提供了一套可视化工具，可从蛋白质或修饰为中心的角度探索染色质调控回路。
{"title":"Decoding the language of chromatin modifications with MARCS","authors":"Andrey Tvardovskiy, Saulius Lukauskas","doi":"10.1038/s41576-024-00758-2","DOIUrl":"10.1038/s41576-024-00758-2","url":null,"abstract":"In this Tools of the Trade article, Andrey Tvardovskiy and Saulius Lukauskas introduce the web resource MARCS, which offers a set of visualization tools to explore chromatin regulatory circuits from either a protein- or modification-centred perspective.","PeriodicalId":19067,"journal":{"name":"Nature Reviews Genetics","volume":"25 10","pages":"673-674"},"PeriodicalIF":39.1,"publicationDate":"2024-07-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141538283","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-07-01DOI: 10.1038/s41576-024-00750-w
Cole Trapnell
Single-cell and spatial molecular profiling assays have shown large gains in sensitivity, resolution and throughput. Applying these technologies to specimens from human and model organisms promises to comprehensively catalogue cell types, reveal their lineage origins in development and discern their contributions to disease pathogenesis. Moreover, rapidly dropping costs have made well-controlled perturbation experiments and cohort studies widely accessible, illuminating mechanisms that give rise to phenotypes at the scale of the cell, the tissue and the whole organism. Interpreting the coming flood of single-cell data, much of which will be spatially resolved, will place a tremendous burden on existing computational pipelines. However, statistical concepts, models, tools and algorithms can be repurposed to solve problems now arising in genetic and molecular biology studies of development and disease. Here, I review how the questions that recent technological innovations promise to answer can be addressed by the major classes of statistical tools. Single-cell, spatial and multi-omic profiling technologies generate large-scale data that reveal the output of genome-scale experiments across diverse cells, tissues and organisms. Cole Trapnell reviews the underlying core statistical challenges that need to be tackled to harness the power of these technologies and advance our understanding of gene function in health and disease.
{"title":"Revealing gene function with statistical inference at single-cell resolution","authors":"Cole Trapnell","doi":"10.1038/s41576-024-00750-w","DOIUrl":"10.1038/s41576-024-00750-w","url":null,"abstract":"Single-cell and spatial molecular profiling assays have shown large gains in sensitivity, resolution and throughput. Applying these technologies to specimens from human and model organisms promises to comprehensively catalogue cell types, reveal their lineage origins in development and discern their contributions to disease pathogenesis. Moreover, rapidly dropping costs have made well-controlled perturbation experiments and cohort studies widely accessible, illuminating mechanisms that give rise to phenotypes at the scale of the cell, the tissue and the whole organism. Interpreting the coming flood of single-cell data, much of which will be spatially resolved, will place a tremendous burden on existing computational pipelines. However, statistical concepts, models, tools and algorithms can be repurposed to solve problems now arising in genetic and molecular biology studies of development and disease. Here, I review how the questions that recent technological innovations promise to answer can be addressed by the major classes of statistical tools. Single-cell, spatial and multi-omic profiling technologies generate large-scale data that reveal the output of genome-scale experiments across diverse cells, tissues and organisms. Cole Trapnell reviews the underlying core statistical challenges that need to be tackled to harness the power of these technologies and advance our understanding of gene function in health and disease.","PeriodicalId":19067,"journal":{"name":"Nature Reviews Genetics","volume":"25 9","pages":"623-638"},"PeriodicalIF":39.1,"publicationDate":"2024-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141477026","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-06-26DOI: 10.1038/s41576-024-00756-4
Linda Koch
A study in Nature charts the history of malaria in the Americas from ancient Plasmodium parasite genomes.
自然》杂志上的一项研究从古老的疟原虫基因组中描绘了美洲的疟疾历史。
{"title":"Charting the evolutionary history of malaria","authors":"Linda Koch","doi":"10.1038/s41576-024-00756-4","DOIUrl":"10.1038/s41576-024-00756-4","url":null,"abstract":"A study in Nature charts the history of malaria in the Americas from ancient Plasmodium parasite genomes.","PeriodicalId":19067,"journal":{"name":"Nature Reviews Genetics","volume":"25 8","pages":"530-530"},"PeriodicalIF":39.1,"publicationDate":"2024-06-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141453119","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-06-25DOI: 10.1038/s41576-024-00748-4
Gerd P. Pfeifer, Seung-Gi Jin
DNA damage is a threat to genome integrity and can be a cause of many human diseases, owing to either changes in the chemical structure of DNA or conversion of the damage into a mutation, that is, a permanent change in DNA sequence. Determining the exact positions of DNA damage and ensuing mutations in the genome are important for identifying mechanisms of disease aetiology when characteristic mutations are prevalent and probably causative in a particular disease. However, this approach is challenging particularly when levels of DNA damage are low, for example, as a result of chronic exposure to environmental agents or certain endogenous processes, such as the generation of reactive oxygen species. Over the past few years, a comprehensive toolbox of genome-wide methods has been developed for the detection of DNA damage and rare mutations at single-nucleotide resolution in mammalian cells. Here, we review and compare these methods, describe their current applications and discuss future research questions that can now be addressed. In this Review, Pfeifer and Jin discuss currently available methods for genome-wide mapping of DNA damage and rare mutations and illustrate how these technologies are being used to study mechanisms of mutagenesis linked to the aetiology of human diseases.
DNA 损伤是对基因组完整性的一种威胁，也可能是许多人类疾病的病因，其原因是 DNA 的化学结构发生变化或损伤转化为突变，即 DNA 序列发生永久性变化。当特征性突变普遍存在并可能导致某种疾病时，确定基因组中 DNA 损伤和随之而来的突变的确切位置对于确定疾病的病因机制非常重要。然而，这种方法具有挑战性，尤其是在 DNA 损伤水平较低的情况下，例如，由于长期暴露于环境因子或某些内源过程（如活性氧的产生）而导致的损伤。在过去几年中，人们开发出了一套全面的全基因组方法工具箱，用于以单核苷酸分辨率检测哺乳动物细胞中的 DNA 损伤和罕见突变。在此，我们回顾并比较了这些方法，介绍了它们目前的应用情况，并讨论了现在可以解决的未来研究问题。
{"title":"Methods and applications of genome-wide profiling of DNA damage and rare mutations","authors":"Gerd P. Pfeifer, Seung-Gi Jin","doi":"10.1038/s41576-024-00748-4","DOIUrl":"10.1038/s41576-024-00748-4","url":null,"abstract":"DNA damage is a threat to genome integrity and can be a cause of many human diseases, owing to either changes in the chemical structure of DNA or conversion of the damage into a mutation, that is, a permanent change in DNA sequence. Determining the exact positions of DNA damage and ensuing mutations in the genome are important for identifying mechanisms of disease aetiology when characteristic mutations are prevalent and probably causative in a particular disease. However, this approach is challenging particularly when levels of DNA damage are low, for example, as a result of chronic exposure to environmental agents or certain endogenous processes, such as the generation of reactive oxygen species. Over the past few years, a comprehensive toolbox of genome-wide methods has been developed for the detection of DNA damage and rare mutations at single-nucleotide resolution in mammalian cells. Here, we review and compare these methods, describe their current applications and discuss future research questions that can now be addressed. In this Review, Pfeifer and Jin discuss currently available methods for genome-wide mapping of DNA damage and rare mutations and illustrate how these technologies are being used to study mechanisms of mutagenesis linked to the aetiology of human diseases.","PeriodicalId":19067,"journal":{"name":"Nature Reviews Genetics","volume":"25 12","pages":"846-863"},"PeriodicalIF":39.1,"publicationDate":"2024-06-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141448131","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-06-25DOI: 10.1038/s41576-024-00746-6
Yishay Pinto, Ami S. Bhatt
Microbiomes occupy a range of niches and, in addition to having diverse compositions, they have varied functional roles that have an impact on agriculture, environmental sciences, and human health and disease. The study of microbiomes has been facilitated by recent technological and analytical advances, such as cheaper and higher-throughput DNA and RNA sequencing, improved long-read sequencing and innovative computational analysis methods. These advances are providing a deeper understanding of microbiomes at the genomic, transcriptional and translational level, generating insights into their function and composition at resolutions beyond the species level. In this Review, Pinto and Bhatt provide an overview of DNA-sequencing and RNA-sequencing approaches that can be used to study the composition, structure, and function of microbiomes and discuss the biological insights they provide.
微生物群占据着一系列的生态位，除了具有不同的组成之外，它们还具有不同的功能作用，对农业、环境科学以及人类健康和疾病都有影响。最近的技术和分析进步促进了微生物组的研究，如更便宜、更高通量的 DNA 和 RNA 测序、改进的长读数测序和创新的计算分析方法。这些进步使人们在基因组、转录和翻译层面上对微生物组有了更深入的了解，从而对微生物组的功能和组成有了超越物种层面的认识。
{"title":"Sequencing-based analysis of microbiomes","authors":"Yishay Pinto, Ami S. Bhatt","doi":"10.1038/s41576-024-00746-6","DOIUrl":"10.1038/s41576-024-00746-6","url":null,"abstract":"Microbiomes occupy a range of niches and, in addition to having diverse compositions, they have varied functional roles that have an impact on agriculture, environmental sciences, and human health and disease. The study of microbiomes has been facilitated by recent technological and analytical advances, such as cheaper and higher-throughput DNA and RNA sequencing, improved long-read sequencing and innovative computational analysis methods. These advances are providing a deeper understanding of microbiomes at the genomic, transcriptional and translational level, generating insights into their function and composition at resolutions beyond the species level. In this Review, Pinto and Bhatt provide an overview of DNA-sequencing and RNA-sequencing approaches that can be used to study the composition, structure, and function of microbiomes and discuss the biological insights they provide.","PeriodicalId":19067,"journal":{"name":"Nature Reviews Genetics","volume":"25 12","pages":"829-845"},"PeriodicalIF":39.1,"publicationDate":"2024-06-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141448320","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-06-24DOI: 10.1038/s41576-024-00755-5
Linda Koch
Petrazzini et al. leverage exome sequencing data and a novel machine learning-based marker to identify rare and ultra-rare coding variants associated with coronary artery disease.
{"title":"A digital marker for coronary artery disease","authors":"Linda Koch","doi":"10.1038/s41576-024-00755-5","DOIUrl":"10.1038/s41576-024-00755-5","url":null,"abstract":"Petrazzini et al. leverage exome sequencing data and a novel machine learning-based marker to identify rare and ultra-rare coding variants associated with coronary artery disease.","PeriodicalId":19067,"journal":{"name":"Nature Reviews Genetics","volume":"25 8","pages":"529-529"},"PeriodicalIF":39.1,"publicationDate":"2024-06-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141444880","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-06-19DOI: 10.1038/s41576-024-00751-9
Tandem repeats are ubiquitous in the human genome and hold crucial information about our genetic diversity, evolution and susceptibility to disease.
串联重复序列在人类基因组中无处不在，掌握着有关人类遗传多样性、进化和疾病易感性的重要信息。
{"title":"Tandem repeats in the long-read sequencing era","authors":"","doi":"10.1038/s41576-024-00751-9","DOIUrl":"10.1038/s41576-024-00751-9","url":null,"abstract":"Tandem repeats are ubiquitous in the human genome and hold crucial information about our genetic diversity, evolution and susceptibility to disease.","PeriodicalId":19067,"journal":{"name":"Nature Reviews Genetics","volume":"25 7","pages":"449-449"},"PeriodicalIF":42.7,"publicationDate":"2024-06-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.nature.com/articles/s41576-024-00751-9.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141425281","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"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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