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| 1 | Identification of mecciRNAs and their roles in the mitochondrial entry of proteins显示文摘Mammalian mitochondria have small genomes encoding very limited numbers of proteins.Over one thousand proteins and noncoding RNAs encoded by the nuclear genome must be imported from the cytosol into the mitochondria.Here,we report the identification of hundreds of circular RNAs(mecciRNAs)encoded by the mitochondrial genome.We 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 proteins.Known components involved in mitochondrial protein and RNA importation,such as TOM40 and PNPASE,interact with mecciRNAs and regulate protein entry.The 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 importation.mecciRNAs 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. | 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 | 2020 | Science China(Life Sciences)2020，63，10： | 15 |
| 2 | Multivalent m^6A motifs promote phase separation of YTHDF proteins显示文摘Dear Editor,Posttranscriptional modifications of coding and non-coding RNAs are prevale nt in cells.N6-methylade no sine (m6A) is the most abundant type of modification on eukaryotic messenger RNAs (mRNAs).1 This modification plays important roles in multiple fundamental biological processes, for example, cell differentiation, tissue development and tumorigenesis. | Yifei Gao Gaofeng Pei Dongxue Li Ru Li Yanqiu Shao Qiangfeng Cliff Zhang Pilong Li | 2019 | Cell Research2019，29，9： | 7 |
| 3 | Predicting dynamic cellular protein–RNA interactions by deep learning using in vivo RNA structures显示文摘Interactions with RNA-binding proteins(RBPs)are integral to RNA function and cellular regulation,and dynamically reflect specific cellular conditions.However,presently available tools for predicting RBP–RNA interactions employ RNA sequence and/or predicted RNA structures,and therefore do not capture their condition-dependent nature.Here,after profiling transcriptome-wide in vivo RNA secondary structures in seven cell types,we developed PrismNet,a deep learning tool that integrates experimental in vivo RNA structure data and RBP binding data for matched cells to accurately predict dynamic RBP binding in various cellular conditions.PrismNet results for 168 RBPs support its utility for both understanding CLIP-seq results and largely extending such interaction data to accurately analyze additional cell types.Further,PrismNet employs an“attention”strategy to computationally identify exact RBP-binding nucleotides,and we discovered enrichment among dynamic RBP-binding sites for structure-changing variants(riboSNitches),which can link genetic diseases with dysregulated RBP bindings.Our rich profiling data and deep learning-based prediction tool provide access to a previously inaccessible layer of cell-type-specific RBP–RNA interactions,with clear utility for understanding and treating human diseases. | Lei Sun Kui Xu Wenze Huang Yucheng T.Yang Pan Li Lei Tang Tuanlin Xiong Qiangfeng Cliff Zhang | 2021 | Cell Research2021，31，5： | 6 |
| 4 | Comparison of viral RNA-host protein interactomes across pathogenic RNA viruses informs rapid antiviral drug discovery for SARS-CoV-2显示文摘In contrast to the extensive research about viral protein–host protein interactions that has revealed major insights about how RNA viruses engage with host cells during infection,few studies have examined interactions between host factors and viral RNAs(vRNAs).Here,we profiled vRNA–host protein interactomes for three RNA virus pathogens(SARS-CoV-2,Zika,and Ebola viruses)using ChIRP-MS.Comparative interactome analyses discovered both common and virus-specific host responses and vRNA-associated proteins that variously promote or restrict viral infection.In particular,SARS-CoV-2 binds and hijacks the host factor IGF2BP1 to stabilize vRNA and augment viral translation.Our interactome-informed drug repurposing efforts identified several FDA-approved drugs(e.g.,Cepharanthine)as broad-spectrum antivirals in cells and hACE2 transgenic mice.A co-treatment comprising Cepharanthine and Trifluoperazine was highly potent against the newly emerged SARS-CoV-2 B.1.351 variant.Thus,our study illustrates the scientific and medical discovery utility of adopting a comparative vRNA-host protein interactome perspective. | Shaojun Zhang Wenze Huang Lili Ren Xiaohui Ju Mingli Gong Jian Rao Lei Sun Pan Li Qiang Ding Jianwei Wang Qiangfeng Cliff Zhang | 2022 | Cell Research2022，32，1： | 5 |
| 5 | RNA Regulations and Functions Decoded by Transcriptome-wide RNA Structure Probing显示文摘RNA folds into intricate structures that are crucial for its functions and regulations. To date, a multitude of approaches for probing structures of the whole transcriptome, i.e., RNA structuromes, have been developed. Applications of these approaches to different cell lines and tissues have generated a rich resource for the study of RNA structure–function relationships at a systems biology level. In this review, we first introduce the designs of these methods and their applications to study different RNA structuromes. We emphasize their technological differences especially their unique advantages and caveats. We then summarize the structural insights in RNA functions and regulations obtained from the studies of RNA structuromes. And finally, we propose potential directions for future improvements and studies. | meiling piao lei sun qiangfeng cliff zhang | 2017 | Genomics, Proteomics & Bioinformatics2017，15，5： | 3 |
| 6 | Prediction and differential analysis of RNA secondary structure显示文摘Background:RNA structure is the crucial basis for RNA function in various cellular processes.Over the last decade,high throughput structure profiling(SP)experiments have brought enormous insight into RNA secondary structure.Results:In this review,we first provide an overview of approaches for RNA secondary structure prediction,including free energy-based algorithms and comparative sequence analysis.Then we introduce SP technologies,databases to document SP data,and pipelines/algorithms to normalize and interpret SP data.Computational frameworks that incorporate SP data in RNA secondary structure prediction are also presented.Conclusions:We finally discuss potential directions for improvement in the prediction and differential analysis of RNA secondary structure. | Bo Yu Yao Lu Qiangfeng Cliff Zhang Lin Hou | 2020 | Quantitative Biology2020，8，2： | 1 |
| 7 | RNA Structural Dynamics Modulate EGFR-TKI Resistance Through Controlling YRDC Translation in NSCLC Cells显示文摘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 EGFRTKIs-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 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 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. | Boyang Shi Ke An Yueqin Wang Yuhan Fei Caixia Guo Qiangfeng Cliff Zhang Yun-Gui Yang Xin Tian Quancheng Kan | 2023 | Genomics, Proteomics & Bioinformatics2023，21，4： | 1 |
| 8 | Epitranscriptomic technologies and analyses显示文摘RNA can interact with RNA-binding proteins(RBPs),mRNA,or other non-coding RNAs(ncRNAs)to form complex regulatory networks.High-throughput CLIP-seq,degradome-seq,and RNA-RNA interactome sequencing methods represent powerful approaches to identify biologically relevant ncRNA-target and protein-ncRNA interactions.However,assigning ncRNAs to their regulatory target genes or interacting RNA-binding proteins(RBPs)remains technically challenging.Chemical modifications to mRNA also play important roles in regulating gene expression.Investigation of the functional roles of these modifications relies highly on the detection methods used.RNA structure is also critical at nearly every step of the RNA life cycle.In 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 ncRNAs.We also summarize methods used to detect RNA modifications and to probe RNA structure. | Xiaoyu Li Qiao-Xia Liang Jin-Ran Lin Jinying Peng Jian-Hua Yang Chengqi Yi Yang Yu Qiangfeng Cliff Zhang Ke-Ren Zhou | 2020 | Science China(Life Sciences)2020，63，4： | 1 |
| 9 | Recent advances in RNA structurome显示文摘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. | 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 | 2022 | Science China(Life Sciences)2022，65，7： | 1 |
| 10 | 人源Dicer蛋白及其结合pre-miRNA底物复合物的冷冻电镜结构研究显示文摘文章简介人源Dicer蛋白属于RNase III家族成员,由多个结构域组成。人源Dicer蛋白能够识别结合内源性和外源性的小RNA前体,并加工生成长度约为22nt的小RNA。 | 刘忠民 王家 Hang Cheng Xin Ke Lei Sun Qiangfeng Cliff Zhang 王宏伟 | 2019 | 科学新闻2019，0，2： | 0 |
| 11 | IRIS:A method for predicting in vivo RNA secondary structures using PARIS data显示文摘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 enigmatic.PARIS(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 vivo.However,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 resolution.Methods:We introduce IRIS,a method for predicting RNA secondary structure ensembles based on PARIS data.IRIS 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 data.Results:The predicted RNA structure ensembles by IRIS have been verified based on evolutionary conservation information and consistency with other experimental RNA structural data.HIS is implemented in Python and freely available at http://iris.zhanglab.net.Conclusion:IRIS capitalizes upon PARIS data to improve the prediction of in vivo RNA secondary structure ensembles.We expect that IRIS will enhance the application of the PARIS technology and shed more insight on in vivo RNA secondary structures. | Jianyu Zhou Pan Li Wanwen Zeng Wenxiu Ma Zhipeng Lu Rui Jiang Qiangfeng Cliff Zhang Tao Jiang | 2020 | Quantitative Biology2020，8，4： | 0 |
| 12 | RNA structure determination:From 2D to 3D显示文摘RNA molecules serve a wide range of functions that are closely linked to their structures.The basic structural units of RNA consist of single-and double-stranded regions.In order to carry out advanced functions such as catalysis and ligand binding,certain types of RNAs can adopt higher-order structures.The analysis of RNA structures has progressed alongside advancements in structural biology techniques,but it comes with its own set of challenges and corresponding solutions.In 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 scattering.Often,a combination of multiple techniques is employed for the integrated analysis of RNA structures.We also survey important RNA structures that have been recently determined using various techniques. | Jie Deng Xianyang Fang Lin Huang Shanshan Li Lilei Xu Keqiong Ye Jinsong Zhang Kaiming Zhang Qiangfeng Cliff Zhang | 2023 | Fundamental Research2023，3，5： | 0 |
| 13 | A paternal protein facilitates sperm RNA delivery to regulate zygotic development显示文摘Sperm contributes essential paternal factors,including the paternal genome,centrosome,and oocyte-activation signals,to sexual reproduction.However,it remains unresolved how sperm contributes its RNA molecules to regulate early embryonic development.Here,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 localize.We 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 separation.Loss 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 development.These 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. | Dongdong Li Shijing Huang Yongping Chai Ruiqian Zhao Jing Gong Qiangfeng Cliff Zhang Guangshuo Ou Wenyu Wen | 2023 | Science China(Life Sciences)2023，66，10： | 0 |
| 14 | An ultra low-input method for global RNA structure probing uncovers Regnase-1-mediated regulation in macrophages显示文摘To enable diverse functions and precise regulation,an RNA sequence often folds into complex yet distinct structures in different cellular states.Probing RNA in its native environment is essential to uncovering RNA structures of biological contexts.However,current methods generally require large amounts of input RNA and are challenging for physiologically relevant use.Here,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 construction.Using 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 responses.These 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. | 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 | 2022 | Fundamental Research2022，2，1： | 0 |
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