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Prediction and differential analysis of RNA secondary structure

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Quantitative Biology 2020年第2期8卷 109-118页

作者： Bo Yu Yao Lu qiangfeng cliff zhang Lin Hou Center for Statistical Science Tsinghua UniversityBeijing 100084China Department of Industrial Engineering Tsinghua UniversityBeijing 100084China School of Life Sciences Tsinghua UniversityBeijing 100084China MOE Key Laboratory of Bioinformatics Tsinghua UniversityBeijing 100084China Beijing Advanced Innovation Center for Structural Biology Center for Synthetic and Systems BiologyTsinghua-Peking Center for Life SciencesTsinghua UniversityBeijing 100084China

Background:RNA structure is the crucial basis for RNA function in various cellular *** the last decade,high throughput structure profiling(SP)experiments have brought enormous insight into RNA secondary ***:In this review,we first provide an overview of approaches for RNA secondary structure prediction,including free energy-based algorithms and comparative sequence *** we introduce SP technologies,databases to document SP data,and pipelines/algorithms to normalize and interpret SP *** frameworks that incorporate SP data in RNA secondary structure prediction are also ***:We finally discuss potential directions for improvement in the prediction and differential analysis of RNA secondary structure.

关键词： RNA secondary structure prediction differential analysis structure profiling

A paternal protein facilitates sperm RNA delivery to regulate zygotic development

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Science China(Life Sciences) 2023年第10期66卷 2342-2353页

作者： Dongdong Li Shijing Huang Yongping Chai Ruiqian Zhao Jing Gong qiangfeng cliff zhang Guangshuo Ou Wenyu Wen Tsinghua-Peking Center for Life Sciences Beijing Frontier Research Center for Biological StructureMcGovern Institute for Brain ResearchSchool of Life Sciences and MOE Key Laboratory for Protein ScienceTsinghua UniversityBeijing 100084China Department of Neurosurgery Huashan Hospitalthe Shanghai Key Laboratory of Medical EpigeneticsInstitutes of Biomedical SciencesState Key Laboratory of Medical Neurobiology and MOE Frontiers Center for Brain ScienceNational Center for Neurological DisordersSchool of Basic Medical SciencesFudan UniversityShanghai 200032China

Sperm contributes essential paternal factors,including the paternal genome,centrosome,and oocyte-activation signals,to sexual ***,it remains unresolved how sperm contributes its RNA molecules to regulate early embryonic ***,we show that the Caenorhabditis elegans paternal protein SPE-11 assembles into granules during meiotic divisions of spermatogenesis and later matures into a perinuclear structure where sperm RNAs *** reconstitute an SPE-11 liquid-phase scaffold in vitro and find that SPE-11 condensates incorporate the nematode RNA,which,in turn,promotes SPE-11 phase *** of SPE-11 does not affect sperm motility or fertilization but causes pleiotropic development defects in early embryos,and spe-11 mutant males reduce m RNA levels of genes crucial for an oocyte-to-embryo transition or embryonic *** results reveal that SPE-11 undergoes phase separation and associates with sperm RNAs that are delivered to oocytes during fertilization,providing insights into how a paternal protein regulates early embryonic development.

关键词： SPE-11 phase separation paternal factor early embryonic development

RNA structure determination:From 2D to 3D

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Fundamental Research 2023年第5期3卷 727-737页

作者： Jie Deng Xianyang Fang Lin Huang Shanshan Li Lilei Xu Keqiong Ye Jinsong zhang Kaiming zhang qiangfeng cliff zhang Guangdong Provincial Key Laboratory of Malignant Tumor Epigenetics and Gene Regulation Guangdong-Hong Kong Joint Laboratory for RNA MedicineSun Yat-Sen Memorial HospitalSun Yat-Sen UniversityGuangzhou 510120China Beijing Frontier Research Center for Biological Structure Center for Synthetic and Systems BiologySchool of Life SciencesTsinghua UniversityBeijing 100084China Key Laboratory of RNA Biology CAS Center for Excellence in BiomacromoleculesInstitute of BiophysicsChinese Academy of SciencesBeijing 100101China MOE Key Laboratory for Cellular Dynamics and Center for Advanced Interdisciplinary Science and Biomedicine of IHM Division of Life Sciences and MedicineUniversity of Science and Technology of ChinaHefei 230027China University of Chinese Academy of Sciences Beijing 100049China MOE Key Laboratory of Bioinformatics Beijing Advanced Innovation Center for Structural Biology&Frontier Research Center for Biological StructureCenter for Synthetic and Systems BiologySchool of Life SciencesTsinghua UniversityBeijing 100084China Tsinghua-Peking Center for Life Sciences Beijing 100084China

RNA molecules serve a wide range of functions that are closely linked to their *** basic structural units of RNA consist of single-and double-stranded *** order to carry out advanced functions such as catalysis and ligand binding,certain types of RNAs can adopt higher-order *** analysis of RNA structures has progressed alongside advancements in structural biology techniques,but it comes with its own set of challenges and corresponding *** this review,we will discuss recent advances in RNA structure analysis techniques,including structural probing methods,X-ray crystallography,nuclear magnetic resonance,cryo-electron microscopy,and small-angle X-ray ***,a combination of multiple techniques is employed for the integrated analysis of RNA *** also survey important RNA structures that have been recently determined using various techniques.

关键词： RNA structure RNA structure probing X-ray crystallography Nuclear magnetic resonance spectroscopy Cryo-electron microscopy Small angle X-ray scattering

RNA Structural Dynamics Modulate EGFR-TKI Resistance Through Controlling YRDC Translation in NSCLC Cells

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Genomics, Proteomics & Bioinformatics 2023年第4期21卷 850-865页

作者： Boyang Shi Ke An Yueqin Wang Yuhan Fei Caixia Guo qiangfeng cliff zhang Yun-Gui Yang Xin Tian Quancheng Kan Department of Pharmacy The First Affiliated Hospital of Zhengzhou UniversityZhengzhou 450052China Henan Key Laboratory of Precision Clinical Pharmacy Zhengzhou UniversityZhengzhou 450052China Key Laboratory of Genomic and Precision Medicine Beijing Institute of GenomicsChinese Academy of Sciences and China National Center for BioinformationBeijing 100101China MOE Key Laboratory of Bioinformatics Center for Synthetic and Systems BiologyBeijing Advanced Innovation Center for Structural BiologyTsinghua-Peking Joint Center for Life SciencesSchool of Life SciencesTsinghua UniversityBeijing 100084China

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 ***,the mechanisms that control the resistance of EGFR-TKIs remain largely *** structures have widespread and crucial functions in many biological regulations;however,the functions of RNA structures in regulating cancer drug resistance remain ***,the psoralen analysis of RNA interactions and structures(PARIS)method is used to establish the higher-order RNA structure maps of EGFRTKIs-resistant and-sensitive cells of *** 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 *** structure formation in YRDC 30 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 *** 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.

关键词： RNA structure EGFR-TKI resistance Non-small cell lung cancer YRDC ELAVL1

IRIS:A method for predicting in vivo RNA secondary structures using PARIS data

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Quantitative Biology 2020年第4期8卷 369-381页

作者： Jianyu Zhou Pan Li Wanwen Zeng Wenxiu Ma Zhipeng Lu Rui Jiang qiangfeng cliff zhang Tao Jiang Bioinformatics Division BNRISTTsinghua UniversityBeijing 100084China Department of Computer Science and Technology Tsinghua UniversityBeijing 100084China MOE Key Laboratory of Bioinformatics Beijing Advanced Innovation Center for Structural BiologyCenter for Synthetic and Systems BiologyTsinghua-Peking Center for Life SciencesSchool of Life SciencesTsinghua UniversityBeijing 100084China College of Software Nankai UniversityTianjin 300071China Department of Statistics University of CaliforniaRiversideCA 92521USA Department of Pharmacology and Pharmaceutical Sciences University of Southern CaliforniaCA 90089USA Department of Automation Tsinghua UniversityBeijing 100084China Department of Computer Science and Engineering University of CaliforniaRiversideCA 92521USA

Background:RNA secondary structures play a pivotal role in posttranscriptional regulation and the functions of non-coding RNAs,yet in vivo RNA secondary structures remain ***(Psoralen Analysis of RNA Interactions and Structures)is a recently developed high-throughput sequencing-based approach that enables direct capture of RNA duplex structures in ***,the existence of incompatible,fuzzy pairing information obstructs the integration of PARIS data with the existing tools for reconstructing RNA secondary structure models at the single-base ***:We introduce IRIS,a method for predicting RNA secondary structure ensembles based on PARIS *** generates a large set of candidate RNA secondary structure models under the guidance of redistributed PARIS reads and then uses a Bayesian model to identify the optimal ensemble,according to both thermodynamic principles and PARIS ***:The predicted RNA structure ensembles by IRIS have been verified based on evolutionary conservation information and consistency with other experimental RNA structural *** is implemented in Python and freely available at http://***:IRIS capitalizes upon PARIS data to improve the prediction of in vivo RNA secondary structure *** expect that IRIS will enhance the application of the PARIS technology and shed more insight on in vivo RNA secondary structures.

关键词： RNA secondary structure PARIS data in vivo structure ensembles incompatible reads

Epitranscriptomic technologies and analyses

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Science China(Life Sciences) 2020年第4期63卷 501-515页

作者： Xiaoyu Li Qiao-Xia Liang Jin-Ran Lin Jinying Peng Jian-Hua Yang Chengqi Yi Yang Yu qiangfeng cliff zhang Ke-Ren Zhou State Key Laboratory of Protein and Plant Gene Research School of Life SciencesPeking UniversityBeijing 100871China MOE Key Laboratory of Gene Function and Regulation State Key Laboratory for BiocontrolSchool of Life SciencesSun Yat-Sen UniversityGuangzhou 510275China The Fifth Affiliated Hospital Sun Yat-Sen UniversityZhuhai 519000China Department of Chemical Biology and Synthetic and Functional Biomolecules Center College of Chemistry and Molecular EngineeringPeking UniversityBeijing 100871China Key Laboratory of RNA Biology CAS Center for Excellence in BiomacromoleculesInstitute of BiophysicsChinese Academy of SciencesBeijing 100101 China MOE Key Laboratory of Bioinformatics Beijing Advanced Innovation Center for Structural BiologyCenter for Synthetic and Systems BiologyTsinghua-Peking Joint Center for Life SciencesSchool of Life SciencesTsinghua UniversityBeijing 100084China

RNA can interact with RNA-binding proteins(RBPs),mRNA,or other non-coding RNAs(ncRNAs)to form complex regulatory ***-throughput CLIP-seq,degradome-seq,and RNA-RNA interactome sequencing methods represent powerful approaches to identify biologically relevant ncRNA-target and protein-ncRNA ***,assigning ncRNAs to their regulatory target genes or interacting RNA-binding proteins(RBPs)remains technically *** modifications to mRNA also play important roles in regulating gene *** of the functional roles of these modifications relies highly on the detection methods *** structure is also critical at nearly every step of the RNA life *** this review,we summarize recent advances and limitations in CLIP technologies and discuss the computational challenges of and bioinformatics tools used for decoding the functions and regulatory networks of *** also summarize methods used to detect RNA modifications and to probe RNA structure.

关键词： ncRNA bioinformatics CLIP-seq RNA modification quantification and locus-specific detection methods transcriptome-wide sequencing technologies RNA structuromes RNA structure probing methods

Identification of mecciRNAs and their roles in the mitochondrial entry of proteins

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Science China(Life Sciences) 2020年第10期63卷 1429-1449页

作者： Xu Liu Xiaolin Wang Jingxin Li Shanshan Hu Yuqi Deng Hao Yin Xichen Bao qiangfeng cliff zhang Geng Wang Baolong Wang Qinghua Shi Ge Shan Deparment of Clinical Laboratory The Firs Ajiaued Hospital of USICHefei National Laborarory for Physical Sciences an Microscalethe CAS Key Laboratory of Inmate Immunity and Chronic DiseaseSchool of Basic Medical SciencesDivision of Life Science and MedicineUniversity of Science and Technology of ChinaHefei 230027China Department of Neurosurgery The First Afiliated Hospial of University of Science and Technology of China Hefei 230001China Key Laboratory of Regeneralive Biology of the Chinese Academy of Sciences Joint School of Life SciencesGuangzhou Medical Untiversily and Guangzhou Institutes of Biomedicine and HealhChinese Academy of SciencesGuangzhou 510530China MOE Key Laboratory of Bioinformatics School of Life SciencesTsinghua UniversiyBeiing 100084.China CAS Center for Excellence in Molecular Cell Science Shanghai Institute of Biochemistry and Cell BiologyChinese Academy of SciencesShanghai 200031China

Mammalian mitochondria have small genomes encoding very limited numbers of *** one thousand proteins and noncoding RNAs encoded by the nuclear genome must be imported from the cytosol into the ***,we report the identification of hundreds of circular RNAs(mecciRNAs)encoded by the mitochondrial *** provide both in vitro and in vivo evidence to show that mecciRNAs facilitate the mitochondrial entry of nuclear-encoded proteins by serving as molecular chaperones in the folding of imported *** components involved in mitochondrial protein and RNA importation,such as TOM40 and PNPASE,interact with mecciRNAs and regulate protein *** expression of mecciRNAs is regulated,and these transcripts are critical for the adaption of mitochondria to physiological conditions and diseases such as stresses and cancers by modulating mitochondrial protein *** and their associated physiological roles add categories and functions to the known eukaryotic circular RNAs and shed novel light on the communication between mitochondria and the nucleus.

关键词： mitochondria circRNA mecciRNA mitochondrial protein import

An ultra low-input method for global RNA structure probing uncovers Regnase-1-mediated regulation in macrophages

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Fundamental Research 2022年第1期2卷 2-13页

作者： Meiling Piao Pan Li Xiaomin Zeng Xi-Wen Wang Lan Kang Jinsong zhang Yifan Wei Shaojun zhangas Lei Tang Jianghui Zhu Chun Kit Kwok Xiaoyu Hu qiangfeng cliff zhang MOE Key Laboratory of Bioinformatics Center for Synthetic and Systems BiologySchool of Life SciencesTsinghua UniversityBeijing 100084China Beijing Advanced Innovation Center for Structural Biology&Frontier Research Center for Biological Structure School of Life SciencesTsinghua UniversityBeijing 100084China Tsinghua-Peking Center for Life Sciences Beijing 100084China Institute for Immunology and School of Medicine Tsinghua UniversityBeijingChina Beijing Key Laboratory for Immunological Research on Chronic Diseases Tsinghua-Peking Center for Life SciencesTsinghua UniversityBeijingChina department of Chemistry City University of Hong KongTat Chee AvenueKowloon TongHong KongChina Shenzhen Research Institute of City University of Hong Kong ShenzhenChina

To enable diverse functions and precise regulation,an RNA sequence often folds into complex yet distinct structures in different cellular *** RNA in its native environment is essential to uncovering RNA structures of biological ***,current methods generally require large amounts of input RNA and are challenging for physiologically relevant ***,we report smartSHAPE,a new RNA structure probing method that requires very low amounts of RNA input due to the largely reduced artefact of probing signals and increased efficiency of library *** smartSHAPE,we showcased the profiling of the RNA structure landscape of mouse intestinal macrophages upon inflammation,and provided evidence that RNA conformational changes regulate immune *** results demonstrate that smartSHAPE can greatly expand the scope of RNA structure-based investigations in practical biological systems,and also provide a research paradigm for the study of post-transcriptional regulation.

关键词： RNA structure probing method Low-input RNA structure element Macrophage RNA structure RNA structurome

Recent advances in RNA structurome

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Science China(Life Sciences) 2022年第7期65卷 1285-1324页

作者： Bingbing Xu Yanda Zhu Changchang Cao Hao Chen Qiongli Jin Guangnan Li Junfeng Ma Siwy Ling Yang Jieyu Zhao Jianghui Zhu Yiliang Ding Xianyang Fang Yongfeng Jin Chun Kit Kwok Aiming Ren Yue Wan Zhiye Wang Yuanchao Xue Huakun zhang qiangfeng cliff zhang Yu Zhou MOE Laboratory of Biosystems Homeostasis&Protection Innovation Center for Cell Signaling NetworkCollege of Life SciencesZhejiang UniversityHangzhou 310058China Key Laboratory of RNA Biology Institute of BiophysicsChinese Academy of SciencesBeijing 100101China Life Sciences Institute Zhejiang UniversityHangzhou 310058China State Key Laboratory of Plant Physiology and Biochemistry College of Life SciencesZhejiang UniversityHangzhou 310058China State Key Laboratory of Virology College of Life SciencesWuhan UniversityWuhan 430072China Beijing Advanced Innovation Center for Structural Biology School of Life SciencesTsinghua UniversityBeijing 100084China Stem Cell and Regenerative Biology Genome Institute of SingaporeA*STARSingaporeSingapore Department of Chemistry and State Key Laboratory of Marine PollutionCity University of Hong KongHong KongChina MOE Key Laboratory of Bioinformatics Beijing Advanced Innovation Center for Structural Biology and Frontier Research Center for Biological StructureCenter for Synthetic and Systems BiologySchool of Life SciencesTsinghua UniversityBeijing 100084China Tsinghua-Peking Center for Life Sciences Beijing 100084China Department of Cell and Developmental Biology John Innes CentreNorwich Research ParkNorwich NR47UHUnited Kingdom Shenzhen Research Institute of City University of Hong Kong Shenzhen 518057China University of Chinese Academy of Sciences Beijing 100101China Key Laboratory of Molecular Epigenetics of the Ministry of Education Northeast Normal UniversityChangchun 130024China

RNA structures are essential to support RNA functions and regulation in various biological processes. Recently, a range of novel technologies have been developed to decode genome-wide RNA structures and novel modes of functionality across a wide range of species. In this review, we summarize key strategies for probing the RNA structurome and discuss the pros and cons of representative technologies. In particular, these new technologies have been applied to dissect the structural landscape of the SARS-CoV-2 RNA genome. We also summarize the functionalities of RNA structures discovered in different regulatory layers-including RNA processing, transport, localization, and mRNA translation-across viruses, bacteria, animals, and plants. We review many versatile RNA structural elements in the context of different physiological and pathological processes(e.g., cell differentiation, stress response, and viral replication). Finally, we discuss future prospects for RNA structural studies to map the RNA structurome at higher resolution and at the single-molecule and single-cell level, and to decipher novel modes of RNA structures and functions for innovative applications.

关键词： RNA structurome high-throughput techniques genome-wide 3D structure RNA secondary structure SARS-CoV-2 decoding function

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