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1Manipulating mRNA splicing by base editing in plants显示文摘Precursor-mRNAs(pre-mRNA) can be processed into one or more mature m RNA isoforms through constitutive or alternative splicing pathways. Constitutive splicing of pre-mRNA plays critical roles in gene expressional regulation, such as intronmediated enhancement(IME), whereas alternative splicing(AS) dramatically increases the protein diversity and gene functional regulation. However, the unavailability of mutants for individual spliced isoforms in plants has been a major limitation in studying the function of mRNA splicing. Here, we describe an efficient tool for manipulating the splicing of plant genes. Using a Cas9-directed base editor, we converted the 5′ splice sites in four Arabidopsis genes from the activated GT form to the inactive AT form. Silencing the AS of HAB 1.1(encoding a type 2 C phosphatase) validated its function in abscisic acid signaling, while perturbing the AS of RS31 A revealed its functional involvement in plant response to genotoxic treatment for the first time. Lastly,altering the constitutive splicing of Act2 via base editing facilitated the analysis of IME. This strategy provides an efficient tool for investigating the function and regulation of gene splicing in plants and other eukaryotes.Chenxiao Xue Huawei Zhang Qiupeng Lin Rong Fan Caixia Gao 2018Science China(Life Sciences)2018,61,11:18
2Fine-Tuning of MiR528 Accumulation Modulates Flowering Time in Rice显示文摘In plants,microRNA (miRNA) functions in the post-transcriptional repression of target mRNAs have been well explored.However,the mechanisms regulating the accumulation of miRNAs remain poorly under.stood.Here,we report that distinct mechanisms regulate accumulation of a monocot-specific miRNA,rice (Oryza sativa) miR528.At the transcriptional level,miR528 accumulated to higher levels in older plants than in young seedlings and exhibited aging-modulated gradual accumulation and diurnal rhythms in leaves;at the post-transcriptional level,aging also modulated miR528 levels by enhancing pri-miR528 alter.native splicing.We found that miR528 promotes rice flowering under long-day conditions by targeting RED AND FAR-RED INSENSITIVE2 (OsRFI2).Moreover,natural variations in the MIR528 promoter region caused differences in miR528 expression among rice varieties,which are correlated with their different binding affinities with the transcription factor OsSPL9 that activates the expression of miR528.Taken together,our findings reveal rice plants have evolved sophisticated modes fine-tuning miR528 levels and provide insight into the mechanisms that regulate MIRNA expression in plants.Rongxin Yang Pingchuan Li Hailiang Mei Dong Wang Jing Sun Chao Yang Lili Hao Shouyun Cao Chengcai Chu Songnian Hu Xianwei Song Xiaofeng Cao 2019Molecular Plant2019,12,8:12
3Dek42 encodes an RNA-binding protein that affects alternative pre-m RNA splicing and maize kernel development显示文摘RNA-binding proteins (RBPs) play an important role in post-transcriptional gene regulation. However, the functions of RBPs in plants remain poorly understood. Maize kernel mutant dek42 has small defective kernels and lethal seedlings. Dek42 was cloned by Mutator tag isolation and further confirmed by an independent mutant allele and clustered regularly interspaced short palindromic repeats (CRISPR)-CRISPR-associated protein 9 materials. Dek42 encodes an RRM_RBM48 type RNA-binding protein that localizes to the nucleus. Dek42 is constitutively expressed in various maize tissues. The dek42 mutation caused a significant reduction in the accumulation of DEK42 protein in mutant kernels. RNA-seq analysis showed that the dek42 mutation significantly disturbed the expression of thousands of genes during maize kernel development. Sequence analysis also showed that the dek42 mutation significantly changed alternative splicing in expressed genes, which were especially enriched for the U12-type intron-retained type. Yeast two-hybrid screening identified SF3a1 as a DEK42-interacting protein. DEK42 also interacts with the spliceosome component U1-70K. These results suggested that DEK42 participates in the regulation of pre-messenger RNA splicing through its interaction with other spliceosome components. This study showed the function of a newly identified RBP and provided insights into alternative splicing regulation during maize kernel development.Yi Zuo Fan Feng Weiwei Qi Rentao Song 2019Journal of Integrative Plant Biology2019,61,6:7
4Regulation of mammalian pre-mRNA splicing显示文摘In eukaryotes,most protein-coding genes contain introns which are removed by precursor messenger RNA(pre-mRNA) splicing.Alternative splicing is a process by which multiple messenger RNAs(mRNAs) are generated from a single pre-mRNA,resulting in functionally distinct proteins.Recent genome-wide analyses of alternative splicing indicated that in higher eukaryotes alternative splicing is an important mechanism that generates proteomic complexity and regulates gene expression.Mis-regulation of splicing causes a wide range of human diseases.This review describes the current understanding of pre-mRNA splicing and the mechanisms that regulate mammalian pre-mRNA splicing.It also discusses emerging directions in the field of alternative splicing.HUI JingYi State Key Laboratory of Molecular Biology,Institute of Biochemistry and Cell Biology,Shanghai Institutes for Biological Sciences,Chinese Academy of Sciences,Shanghai 200031,China 2009Science China(Life Sciences)2009,52,3:6
5Splicing dysregulation in cancer: from mechanistic understanding to a new class of therapeutic targets显示文摘RNA splicing dysregulation is widespread in cancer. Accumulating evidence demonstrates that splicing defects resulting from splicing dysregulation play critical roles in cancer pathogenesis and can serve as new biomarkers and therapeutic targets for cancer intervention. These findings have greatly deepened the mechanistic understandings of the regulation of alternative splicing in cancer cells, leading to rapidly growing interests in targeting cancer-related splicing defects as new therapies. Here we summarize the current research progress on splicing dysregulation in cancer and highlight the strategies available or under development for targeting RNA splicing defects in cancer.Yongbo Wang Yufang Bao Sirui Zhang Zefeng Wang 2020Science China(Life Sciences)2020,63,4:5
6Phytophthora Effectors Modulate Genome-wide Alternative Splicing of Host mRNAs to Reprogram Plant Immunity显示文摘Alternative splicing(AS)of pre-mRNAs increases transcriptome and proteome diversity,regulates gene expression through multiple mechanisms,and plays important roles in plant development and stress responses.However,the prevalence of genome-wide plant AS changes during infection and the mechanisms by which pathogens modulate AS remain poorly understood.Here,we examined the global AS changes in tomato leaves infected with Phytophthora infestans,the infamous Irish famine pathogen.We show that more than 2000 genes exhibiting significant changes in AS are not differentially expressed,indicating that AS is a distinct layer of transcriptome reprogramming during plant-pathogen interactions.Furthermore,our results show that P.infestans subverts host immunity by repressing the AS of positive regulators of plant immunity and promoting the AS of susceptibility factors.To study the underlying mechanism,we established a luminescence-based AS reporter system in Nicotiana benthamiana to screen pathogen effectors modulating plant AS.We identified nine splicing regulatory effectors(SREs)from 87 P.infestans effectors.Further studies revealed that SRE3 physically binds U1-70K to manipulate the plant AS machinery and subsequently modulates AS-mediated plant immunity.Our study not only unveils genome-wide plant AS reprogramming during infection but also establishes a novel AS screening tool to identify SREs from a wide range of plant pathogens,providing opportunities to understand the splicing regulatory mechanisms through which pathogens subvert plant immunity.Jie Huang Xinyu Lu Hongwei Wu Yuchen Xie Qian Peng Lianfeng Gu Juyou Wu Yuanchao Wang Anireddy SNReddy Suomeng Dong 2020Molecular Plant2020,13,10:4
7Alternative splicing of VEGFA,APP and NUMB genes in colorectal cancer显示文摘AIM:To investigate alternative splicing in vascular endothelial growth factor A(VEGFA),amyloid beta precursor protein(APP),and Numb homolog(NUMB) in colorectal cancer(CRC).METHODS:Real-time quantitative reverse transcriptase polymerase chain reaction(q RT-PCR) and PCRrestriction fragment length polymorphism analyses were performed to detect the expression of VEGFA,APP,and NUMB mR NA in 20 CRC tissues and matched adjacent normal tissues,as well as their alternative splicing variants.RESULTS:q RT-PCR analysis revealed that the expression of APP,NUMB,and VEGFA 165 b m RNA were significantly downregulated,while VEGFA m RNA was upregulated,in CRC tissues(all P < 0.05).PCRrestriction fragment length polymorphism analysis revealed that the expression of VEGFA 165a/b in CRC tissues was significantly higher than in adjacent normal tissues(P < 0.05).Compared with adjacent normal tissues,the expression of NUMB-PRRS in CRC tissues was significantly decreased(P < 0.05),and the expression of NUMB-PRRL was increased(P < 0.05).CONCLUSION:Alternative splicing of VEGFA,APP,and NUMB may regulate the development of CRC,and represent new targets for its diagnosis,prognosis,and treatment.Yi-Jun Zhao Hua-Zhong Han Yong Liang Chen-Zhang Shi Qing-Chao Zhu Jun Yang 2015World Journal of Gastroenterology2015,21,21:4
8Allele-specific expression and alternative splicing in horse×donkey and cattle×yak hybrids显示文摘Divergence of gene expression and alter native splicing is a crucial driving force in the evolution of species;to date, however the molecular mechanism remains unclear. Hybrids of closely related species provide a suitable model to analyze allele-specific expressi on (ASE) and allele-specific alter native splicing (ASS). Analysis of ASE and ASS can uncover the differences in cis-regulatory elements between closely related species, while eliminating interferenee of trans-regulatory elements. Here, we provide a detailed characterization of ASE and ASS from 19 and 10 transcriptome datasets across five tissues from reciprocal-cross hybrids of horsex don key (mule/hi nny) and cattlexyak (dzo), respectively. Results showed that 4.8%-8.7% and 10.8%-16.7% of genes exhibited ASE and ASS, respectively. Notably, IncRNAs and pseudogenes were more likely to show ASE than protein-coding genes. In addition, genes showing ASE and ASS in mule/hinny were found to be involved in the regulation of muscle strength, whereas those of dzo were involved in high-altitude adaptati on. In con clusi on, our study dem on strated that explorati on of genes showing ASE and ASS in hybrids of closely related species is feasible for species evolution research.Yu Wang Shan Gao Yue Zhao Wei-Huang Chen Jun-Jie Shao Ni-Ni Wang Ming Li Guang-Xian Zhou Lei Wang Wen-Jing Shen Jing-Tao Xu Wei-Dong Deng Wen Wang Yu-Lin Chen Yu Jiang 2019Zoological Research2019,40,4:4
9Overexpressed long noncoding RNA CRNDE with distinct alternatively spliced isoforms in multiple cancers显示文摘Alternative splicing is a tightly regulated process that contributes to cancer development.CRNDE is a long noncoding RNA with alternative splicing and is implicated in the pathogenesis of several cancers.However,whether deregulated expression of CRNDE is common and which isoforms are mainly involved in cancers remain unclear.In this study,we report that CRNDE is aberrantly expressed in the majority of solid and hematopoietic malignancies.The investigation of CRNDE expression in normal samples revealed that CRNDE was expressed in a tissue- and cell-specific manner.Further comparison of CRNDE expression in 2938 patient samples from 15 solid and hematopoietic tumors showed that CRNDE was significantly overexpressed in 11 malignancies,including 3 reported and 8 unreported,and also implicated that the overexpressed isoforms differed in various cancer types.Furthermore,anti-cancer drugs could efficiently repress CRNDE overexpression in cancer cell lines and primary samples,and even had different impacts on the expression of CRNDE isoforms.Finally,experimental profiles of 12 alternatively spliced isoforms demonstrated that the spliced variant CRNDE-g was the most highly expressed isoform in multiple cancer types.Collectively,our results emphasize the cancer-associated feature of CRNDE and its spliced isoforms,and may provide promising targets for cancer diagnosis and therapy.Xuefei Ma Wei Zhang Rong Zhang Jingming Li Shufen Li Yunlin Ma Wen Jin Kankan Wang 2019Frontiers of Medicine2019,13,3:3
10Aberrant expression of alternative isoforms of transcription factors in hepatocellular carcinoma显示文摘Hepatocellular carcinoma(HCC) is one of the most prevalent malignancies worldwide and the second leading cause of death among all cancer types. Deregulation of the networks of tissue-specific transcription factors(TFs) observed in HCC leads to profound changes in the hepatic transcriptional program that facilitates tumor progression. In addition, recent reports suggest that substantial aberrations in the production of TF isoforms occur in HCC. In vitro experiments have identified distinct isoform-specific regulatory functions and related biological effects of liver-specific TFs that are implicated in carcinogenesis, which may be relevant for tumor progression and clinical outcome. This study reviews available data on the expression of isoforms of liver-specific and ubiquitous TFs in the liver and HCC and their effects, including HNF4α, C/EBPs, p73 and TCF7 L2, and indicates that assessment of the ratio of isoforms and targeting specific TF variants may be beneficial for the prognosis and treatment of HCC.Olga Krivtsova Anna Makarova Natalia Lazarevich 2018World Journal of Hepatology2018,10,10:3
11Modulators of alternative splicing as novel therapeutics in cancer显示文摘Alternative splicing(AS), the process of removing introns from pre-m RNA and re-arrangement of exons to give several types of mature transcripts, has been described more than 40 years ago. However, until recently, it has not been clear how extensive it is. Genome-wide studies have now conclusively shown that more than 90% of genes are alternatively spliced in humans. This makes AS one of the main drivers of proteomic diversity and, consequently, determinant of cellular function repertoire. Unsurprisingly, given its extent, numerous splice isoforms have been described to be associated with several dise-ases including cancer. Many of them have antagonistic functions, e.g., pro- and anti-angiogenic or pro- and anti-apoptotic. Additionally several splice factors have been recently described to have oncogene or tumour suppressors activities, like SF3B1 which is frequently mutated in myelodysplastic syndromes. Beside the implications for cancer pathogenesis, de-regulated AS is recognized as one of the novel areas of cell biology where therapeutic manipulations may be designed. This editorial discusses the possibilities of manipulation of AS for therapeutic benefit in cancer. Approaches involving the use of oligonucleotides as well as small molecule splicing modulators are presented as well as thoughts on how specificity might be accomplished in splicing therapeutics.Sebastian Oltean 2015World Journal of Clinical Oncology2015,6,5:2
12RNA binding protein 24 deletion disrupts global alternative splicing and causes dilated cardiomyopathy显示文摘RNA splicing contributes to a broad spectrum of posttranscriptional gene regulation during normal development, as well as pathological manifestation of heart diseases. However, the functional role and regulation of splicing in heart failure remain poorly understood. RNA binding protein (RBP), a major component of the splicing machinery, is a critical factor in this process. RNA binding motif protein 24 (RBM24) is a tissue-specific RBP which is highly expressed in human and mouse heart. Previous studies demonstrated the functional role of RBM24 in the embryonic heart development. However, the role of RBM24 in postnatal heart development and heart disease has not been investigated. In this paper, using conditional RBM24 knockout mice, we demonstrated that ablation of RBM24 in postnatal heart led to rapidly progressive dilated cardiomyopathy (DCM), heart failure, and postnatal lethality. Global splicing profiling revealed that RBM24 regulated a network of genes related to cardiac function and diseases. Knockout of RBM24 resulted in misregulation of these splicing transitions which contributed to the subsequent development of cardiomyopathy. Notably, our analysis identified RBM24 as a splice factor that determined the splicing switch of a subset of genes in the sacomeric Z-disc complex, including Titin, the major disease gene of DCM and heart failure. Together, this study identifies regulation of RNA splicing by RBM24 as a potent player in remodeling of heart during postnatal development, and provides novel mechanistic insights to the pathogenesis of DCM.Jing Liu Xu Kong Mengkai Zhang Xiao Yang Xiuqin Xu 2019Protein & Cell2019,10,6:2
13Alternative splicing: An important mechanism in stem cell biology显示文摘Alternative splicing(AS) is an essential mechanism in post-transcriptional regulation and leads to protein diversity. It has been shown that AS is prevalent in metazoan genomes, and the splicing pattern is dynamically regulated in different tissues and cell types, including embryonic stem cells. These observations suggest that AS may play critical roles in stem cell biology. Since embryonic stem cells and induced pluripotent stem cells have the ability to give rise to alltypes of cells and tissues, they hold the promise of future cell-based therapy. Many efforts have been devoted to understanding the mechanisms underlying stem cell selfrenewal and differentiation. However, most of the studies focused on the expression of a core set of transcription factors and regulatory RNAs. The role of AS in stem cell differentiation was not clear. Recent advances in highthroughput technologies have all owed the profiling of dynamic splicing patterns and cis-motifs that are responsible for AS at a genome-wide scale, and provided novel insights in a number of studies. In this review, we discuss some recent findings involving AS and stem cells. An emerging picture from these findings is that AS is integrated in the transcriptional and post-transcriptional networks and together they control pluripotency maintenance and differentiation of stem cells.Kenian Chen Xiaojing Dai Jiaqian Wu 2015World Journal of Stem Cells2015,7,1:1
14Alternative splicing of DNA damage response genes and gastrointestinal cancers显示文摘Alternative splicing,which is a common phenomenon in mammalian genomes,is a fundamental process of gene regulation and contributes to great protein diversity.Alternative splicing events not only occur in the normal gene regulation process but are also closely related to certain diseases including cancer.In this review,we briefly demonstrate the concept of alternative splicing and DNA damage and describe the association of alternative splicing and cancer pathogenesis,focusing on the potential relationship of alternative splicing,DNA damage,and gastrointestinal cancers.We will also discuss whether alternative splicing leads to genetic instability,which is considered to be a driving force for tumorigenesis.Better understanding of the role and mechanism of alternative splicing in tumorigenesis may provide new directions for future cancer studies.Bahityar Rahmutulla Kazuyuki Matsushita Fumio Nomura 2014World Journal of Gastroenterology2014,20,46:1
15Cassava Me RS40 is required for the regulation of plant salt tolerance显示文摘Soil salinity affects the expression of serine/arginine-rich(SR) genes and isoforms by alternative splicing, which in turn regulates the adaptation of plants to stress.We previously identified the cassava spliceosomal component 35 like(SCL) and SR subfamilies, belonging to the SR protein family, which are extensively involved in responses to abiotic stresses.However, the post-transcriptional regulatory mechanism of cassava arginine/serine-rich(RS) subfamily in response to salt stress remains to be explored.In the current study, we identified 37 genes of the RS subfamily from 11 plant species and systematically investigated the transcript levels of the RS40 and RS31 genes under diverse abiotic stress conditions.Subsequently, an analysis of the conserved protein domains revealed that plant RS subfamily genes were likely to preserve their conserved molecular functions and played critical functional roles in responses to abiotic stresses.Importantly, we found that overexpression of MeRS40 in Arabidopsis enhanced salt tolerance by maintaining reactive oxygen species homeostasis and up-regulating the salt-responsive genes.However,overexpression of MeRS40 gene in cassava reduced salt tolerance due to the depression of its endogenous gene expression by negative autoregulation of its own pre-mRNA.Moreover, the MeRS40 protein interacted with MeU1-70Ks(MeU1-70Ka and MeU1-70Kb) in vivo and in vitro, respectively.Therefore, our findings highlight the critical role of cassava SR proteins in responses to salt stress in plants.MA Xiao-wen MA Qiu-xiang MA Mu-qing CHEN Yan-hang GU Jin-bao LI Yang HU Qing LUO Qing-wen WEN Ming-fu ZHANG Peng LI Cong WANG Zhen-yu 2023Journal of Integrative Agriculture2023,22,5:0
16Alternative splicing of FMRl gene in fetal and adult human brain黄涛 李兰英 范钰 VICAIRE Serge 庞智玲 MANDEL Jean-Louis 吴冠芸 沈岩 1998Progress in Natural Science:Materials International1998,8,6:0
17Identification of novel mouse and rat CB1R isoforms and in silico modeling of human CB1R for peripheral cannabinoid therapeutics显示文摘Targeting peripheral CB1R is desirable for the treatment of metabolic syndromes without adverse neuropsychiatric effects.We previously reported a human hCB1b isoform that is selectively enriched in pancreatic beta-cells and hepatocytes,providing a potential peripheral therapeutic hCB1R target.It is unknown whether there are peripherally enriched mouse and rat CB1R(mCB1 and rCB1,respectively)isoforms.In this study,we found no evidence of peripherally enriched rodent CB1 isoforms;however,some mCB1R isoforms are absent in peripheral tissues.We show that the mouse Cnr1 gene contains six exons that are transcribed from a single promoter.We found that mCB1A is a spliced variant of extended exon 1 and protein-coding exon 6;mCB1B is a novel spliced variant containing unspliced exon 1,intron 1,and exon 2,which is then spliced to exon 6;and mCB1C is a spliced variant including all 6 exons.Using RNAscope in situ hybridization,we show that the isoforms mCB1A and mCB1B are expressed at a cellular level and colocalized in GABAergic neurons in the hippocampus and cortex.RT-qPCR reveals that mCB1A and mCB1B are enriched in the brain,while mCB1B is not expressed in the pancreas or the liver.Rat rCB1R isoforms are differentially expressed in primary cultured neurons,astrocytes,and microglia.We also investigated modulation of Cnr1 expression by insulin in vivo and carried out in silico modeling of CB1R with JD5037,a peripherally restricted CB1R inverse agonist,using the published crystal structure of hCB1R.The results provide models for future CB1R peripheral targeting.Qing-Rong Liu Nicholas S.Huang Hong Qu Jennifer F.O′Connell Isabel Gonzalez-Mariscal Sara Santa-Cruz-Calvo Maire E.Doyle Zheng-Xiong.Xi Yun Wang Emmanuel.S.Onaivi Josephine M.Egan 2019Acta Pharmacologica Sinica2019,40,3:0
18CircRNAFisher:a systematic computational approach for de novo circular RNA identification显示文摘Circular RNAs (circRNAs)are emerging species of mRNA splicing products with largely unknown functions.Although several computational pipelines for circRNA identification have been developed,these methods strictly rely on uniquely mapped reads overlapping back-splice junctions.(BSJs)and lack approaches to model the statistical significance of the identified circRNAs.Here, we reported a systematic computational approach to identify circRNAs by simultaneously utilizing BSJ overlapping reads and discordant BSJ spanning reads to identify circRNAs.Moreover,we developed a novel procedure to estimate the P-values of the identified circRNAs.A computational cross-validation and experimental validations demonstrated that our method performed favorably compared to existing circRNA detection tools.We created a standalone tool,CircRNAFisher,to implement the method, which might be valuable to computational and experimental scientists studying circRNAs.Guo-yi Jia Duo-lin Wang Meng-zhu Xue Yu-wei Liu Yu-chen Pei Ying-qun Yang Jing-mei Xu Yan-chun Liang Peng Wang 2019Acta Pharmacologica Sinica2019,40,1:0
19Characterization of full-length transcriptome and mechanisms ofsugar accumulation in Annona squamosa fruit显示文摘Annona squamosa is a multipurpose fruit tree employed in nutritional,medicinal,and industrial fields.Its fruit is significantly enriched in sugars,making it an excellent species to study sugar accumulation in fruit.However,the scarcity of genomic resources hinders genetic studies in this species.This study aimed at generating large-scale genomic resources in A.squamosa and deciphering the molecular basis of its high sugar content.Herein,we sequenced and characterized the full-length transcriptome of A.squamosa fruit using PacBio Iso-seq.In addition,we analyzed the changes in sugar content over five fruit growth and ripening stages,and we applied RNA-sequencing technology to investigate the changes in gene expression related to sugar accumulation.A total of 783,647 circular consensus sequences were generated,from which we obtained 48,209 high-quality,full-length transcripts.Additionally,1,838 transcription factors and 1,768 long non-coding RNAs were detected.Furthermore,we identified 10,400 alternative splicing events from 2,541 unigenes having on average 2–4 isoforms.A total of 15,061 simple sequence repeat(SSR)motifs were discovered and up to three primer pairs were designed for each SSR locus.Sugars mainly accumulate during the ripening stage in A.squamosa.Most of the genes involved in sugar transport and metabolism in the fruit were progressively repressed overgrowth and ripening stages.However,sucrose phosphate synthase involved in sucrose synthesis and more importantly,isoamylase,alpha-amylase,beta-amylase,4-alphaglucanotransferase genes involved in starch degradation displayed positive correlations with sugar accumulation in fruit.Overall,we provide here a high-quality,full-length transcriptome assembly which will facilitate gene discovery and molecular breeding of A.squamosa.We found that starch degradation during fruit ripening was the main channel for sugar accumulation in A.squamosa fruit,and the key genes positively linked to sugar accumulation could be further studied to identify targets for controlling sugar content in A.squamosa fruit.REN FANG WEIXIONG HUANG JINYAN YAO XING LONG JI ZHANG SHUANGYUN ZHOU BIAO DENG WENZHONG TANG ZHENYU AN 2020BIOCELL2020,44,4:0
20Alternative splicing of the FMR1 gene in human tissues of fetal and adult丁侃 李兰英 范钰 许琪 韩富天 朱宁宁 刘恩莉 林炳承 吴冠芸 沈岩 1999Progress in Natural Science:Materials International1999,9,5:0
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