搜索到240篇“ POLYADENYLATION“的相关文章
Disruption of PABPN1 phase separation by SNRPD2 drives colorectal cancer cell proliferation and migration through promoting alternative polyadenylation of CTNNBIP1
2024年
Generally shortened 3′UTR due to alternative polyadenylation(APA)is widely observed in cancer,but its regulation mechanisms for cancer are not well characterized.Here,with profiling of APA in colorectal cancer tissues and poly(A)signal editing,we firstly identified that the shortened 3′UTR of CTNNIBP1 in colorectal cancer promotes cell proliferation and migration.We found that liquid-liquid phase separation(LLPS)of PABPN1 is reduced albeit with higher expression in cancer,and the reduction of LLPS leads to the shortened 3′UTR of CTNNBIP1and promotes cell proliferation and migration.Notably,the splicing factor SNRPD2 upregulated in colorectal cancer,can interact with glutamic-proline(EP)domain of PABPN1,and then disrupt LLPS of PABPN1,which attenuates the repression effect of PABPN1 on the proximal poly(A)sites.Our results firstly reveal a new regulation mechanism of APA by disruption of LLPS of PABPN1,suggesting that regulation of APA by interfering LLPS of 3′end processing factor may have the potential as a new way for the treatment of cancer.
Zhijie HuMengxia LiYufeng ChenLiutao ChenYuting HanChengyong ChenXin LuNan YouYawen LouYingye HuangZhanfeng HuoChao LiuCheng LiangSusu LiuKe DengLiangfu ChenShangwu ChenGuohui WanXiaojian WuYonggui FuAnlong Xu
可变多聚腺苷酸化在肿瘤中的研究进展
2024年
可变多聚腺苷酸化(Alternative Polyadenylation, APA)作为一种转录后调控机制,其在基因表达调控中的作用越来越受到重视。近期的许多研究发现APA在肿瘤的发生发展和耐药机制中发挥着重要作用。本文主要总结了APA在基因表达调控和癌症等疾病中的功能作用和新的APA相关的研究方法和数据库。
周梦浩梁华庚
关键词:肿瘤基因表达调控
mRNA alternative polyadenylation (APA) in regulation of gene expression and diseases被引量:1
2023年
The mRNA polyadenylation plays essential function in regulation of mRNA metabolism.Mis-regulations of mRNA polyadenylation are frequently linked with aberrant gene expression and disease progression.Under the action of polyadenylate polymerase,poly(A)tail is synthesized after the polyadenylation signal(PAS)sites on the mRNAs.Alternative polyadenylation(APA)often occurs in mRNAs with multiple poly(A)sites,producing different 3'ends for transcript variants,and therefore plays important functions in gene expression regulation.In this review,we first summarize the classical process of mRNA 3'-terminal formation and discuss the length control mechanisms of poly(A)innucleus and cytoplasm.Thenwe review the research progress on alternative polyadenylation regulation and the APA site selection mechanism.Finally,we summarize the functional roles of APA in the regulation of gene expression and diseases including cancers.
Siyao GuoShuibin Lin
关键词:POLY(A)
A Survey on Methods for Predicting Polyadenylation Sites from DNA Sequences,Bulk RNA-seq,and Single-cell RNA-seq被引量:1
2023年
Alternative polyadenylation(APA)plays important roles in modulating mRNA stability,translation,and subcellular localization,and contributes extensively to shaping eukaryotic transcriptome complexity and proteome diversity.Identification of poly(A)sites(pAs)on a genomewide scale is a critical step toward understanding the underlying mechanism of APA-mediated gene regulation.A number of established computational tools have been proposed to predict pAs from diverse genomic data.Here we provided an exhaustive overview of computational approaches for predicting pAs from DNA sequences,bulk RNA sequencing(RNA-seq)data,and single-cell RNA sequencing(scRNA-seq)data.Particularly,we examined several representative tools using bulk RNA-seq and scRNA-seq data from peripheral blood mononuclear cells and put forward operable suggestions on how to assess the reliability of pAs predicted by different tools.We also proposed practical guidelines on choosing appropriate methods applicable to diverse scenarios.Moreover,we discussed in depth the challenges in improving the performance of pA prediction and benchmarking different methods.Additionally,we highlighted outstanding challenges and opportunities using new machine learning and integrative multi-omics techniques,and provided our perspective on how computational methodologies might evolve in the future for non-30 untranslated region,tissuespecific,cross-species,and single-cell pA prediction.
Wenbin YeQiwei LianCongting YeXiaohui Wu
关键词:POLYADENYLATIONRNA-SEQ
转录后选择性多聚腺苷酸化调控与糖尿病肾病
2023年
选择性多聚腺苷酸化(alternative polyadenylation,APA)作为重要的转录后调控机制,是真核细胞mRNA成熟过程中,由于不同多聚腺苷酸化信号位点的选择导致一个基因产生多个3’UTR序列长度不同的转录异构体,其中pre-mRNA序列中的顺式调控元件、对应的反式作用因子,例如细胞核中多种酶和蛋白因子等共同参与APA调控。研究发现,APA机制参与多种生理、病理进程,主要通过改变3’UTR序列长度影响对应反式作用因子的调控作用,进而调节mRNA定位、稳定性、翻译效率及蛋白的定位等。本文将系统阐述转录后APA的作用机制和研究现状,并结合新近研究进展,探讨APA在糖尿病肾病研究中的前景。
赵婷婷刘志红
关键词:转录后调控糖尿病肾病
Stress responses of plants through transcriptome plasticity by mRNA alternative polyadenylation
2023年
The sessile nature of plants confines their responsiveness to changing environmental conditions.Gene expression regulation becomes a paramount mechanism for plants to adjust their physiological and morphological behaviors.Alternative polyadenylation(APA)is known for its capacity to augment transcriptome diversity and plasticity,thereby furnishing an additional set of tools for modulating gene expression.APA has also been demonstrated to exhibit intimate associations with plant stress responses.In this study,we review APA dynamic features and consequences in plants subjected to both biotic and abiotic stresses.These stresses include adverse environmental stresses,and pathogenic attacks,such as cadmium toxicity,high salt,hypoxia,oxidative stress,cold,heat shock,along with bacterial,fungal,and viral infections.We analyzed the overarching research framework employed to elucidate plant APA response and the alignment of polyadenylation site transitions with the modulation of gene expression levels within the ambit of each stress condition.We also proposed a general APA model where transacting factors,including poly(A)factors,epigenetic regulators,RNA m6A modification factors,and phase separation proteins,assume pivotal roles in APA related transcriptome plasticity during stress response in plants.
Jiawen ZhouQingshun Quinn Li
Alternative polyadenylation-related genetic variants contribute to bladder cancer risk
2023年
Aberrant alternative polyadenylation(APA)events play an important role in cancers,but little is known about whether APA-related genetic variants contribute to the susceptibility to bladder cancer.Previous genome-wide association study performed APA quantitative trait loci(apaQTL)analyses in bladder cancer,and identified 17955 single nucleotide polymorphisms(SNPs).We found that gene symbols of APA affected by apaQTL-associated SNPs were closely correlated with cancer signaling pathways,high mutational burden,and immune infiltration.Association analysis showed that apaQTL-associated SNPs rs34402449 C>A,rs2683524 C>T,and rs11540872 C>G were significantly associated with susceptibility to bladder cancer(rs34402449:OR=1.355,95%confidence interval[CI]:1.159-1.583,P=1.33×10^(−4);rs2683524:OR=1.378,95%CI:1.164-1.632,P=2.03×10^(−4);rs11540872:OR=1.472,95%CI:1.193-1.815,P=3.06×10^(−4)).Cumulative effect analysis showed that the number of risk genotypes and smoking status were significantly associated with an increased risk of bladder cancer(P_(trend)=2.87×10^(−12)).We found that PRR13,being demonstrated the most significant effect on cell proliferation in bladder cancer cell lines,was more highly expressed in bladder cancer tissues than in adjacent normal tissues.Moreover,the rs2683524 T allele was correlated with shorter 3′untranslated regions of PRR13 and increased PRR13 expression levels.Collectively,our findings have provided informative apaQTL resources and insights into the regulatory mechanisms linking apaQTL-associated variants to bladder cancer risk.
Ting LiuJingjing GuChuning LiMengfan GuoLin YuanQiang LvChao QinMulong DuHaiyan ChuHanting LiuZhengdong Zhang
可选择性多聚腺苷酸化参与的应激调控在结直肠癌发生发展中的作用
2023年
随着中国人群肿瘤发病率和死亡率不断攀升,癌症已成为我国城乡居民的主要死因,其中结直肠癌(colorectal cancer,CRC)是肿瘤相关致死的第二高发疾病。探究CRC发生发展机制、寻找新的肿瘤治疗方式对CRC治疗及预后具有重要意义。CRC发生发展与多种因素密切相关,其中可选择性多聚腺苷酸化(alternative polyadenylation,APA)参与的应激调控在肿瘤发生发展中具有重要作用。文章就APA、应激与CRC的网络关系,RNA结合蛋白参与的APA过程在应激及肿瘤发生发展中的作用进行综述。
陈建胜刘冠群周少飞王天楹
关键词:结直肠癌应激RNA结合蛋白
stAPAminer:Mining Spatial Patterns of Alternative Polyadenylation for Spatially Resolved Transcriptomic Studies被引量:1
2023年
Alternative polyadenylation(APA)contributes to transcriptome complexity and gene expression regulation and has been implicated in various cellular processes and diseases.Singlecell RNA sequencing(scRNA-seq)has enabled the profiling of APA at the single-cell level;however,the spatial information of cells is not preserved in scRNA-seq.Alternatively,spatial transcriptomics(ST)technologies provide opportunities to decipher the spatial context of the transcriptomic landscape.Pioneering studies have revealed potential spatially variable genes and/or splice isoforms;however,the pattern of APA usage in spatial contexts remains unappreciated.In this study,we developed a toolkit called stAPAminer for mining spatial patterns of APA from spatially barcoded ST data.APA sites were identified and quantified from the ST data.In particular,an imputation model based on the k-nearest neighbors algorithm was designed to recover APA signals,and then APA genes with spatial patterns of APA usage variation were identified.By analyzing wellestablished ST data of the mouse olfactory bulb(MOB),we presented a detailed view of spatial APA usage across morphological layers of the MOB.We compiled a comprehensive list of genes with spatial APA dynamics and obtained several major spatial expression patterns that represent spatial APA dynamics in different morphological layers.By extending this analysis to two additional replicates of the MOB ST data,we observed that the spatial APA patterns of several genes were reproducible among replicates.stAPAminer employs the power of ST to explore the transcriptional atlas of spatial APA patterns with spatial resolution.This toolkit is available at https://github.com/BMILAB/stAPAminer and https://ngdc.cncb.ac.cn/biocode/tools/BT007320.
Guoli JiQi TangSheng ZhuJunyi ZhuPengchao YeShuting XiaXiaohui Wu
关键词:IMPUTATION
Alternative polyadenylation events in epithelial cells sense endometritis progression in dairy cows
2023年
Endometritis(inflammation of the endometrial lining) is one of the most devastating reproductive diseases in dairy cattle, resulting in substantial production loss and causing more than $650 million in lost revenue annually in the USA.We hypothesize that alternative polyadenylation(APA) sites serve as decisive sensors for endometrium health and disease in dairy cows. Endometrial cells collected from 18 cows with purulent vaginal discharge scored 0 to 2 were used for APA profiling with our whole transcriptome termini site sequencing(WTTS-seq) method. Overall, pathogens trigger hosts to use more differentially expressed APA(DE-APA), more intronic DE-APA, more DE-APA sites per gene and more DE-genes associated with inflammation. Host CD59 molecule(CD59), Fc fragment of IgG receptor IIa(FCGR2A), lymphocyte antigen 75(LY75) and plasminogen(PLG) may serve as initial contacts or combats with pathogens on cell surface, followed by activation of nuclear receptor subfamily 1 group H member 4(NR1H4) to regulate AXL receptor tyrosine kinase(AXL), FGR proto-oncogene, Src family tyrosine kinase(FGR), HCK protooncogene, Src family tyrosine kinase(HCK) and integrin subunit beta 2(ITGB2) for anti-inflammation. This study is the first to show significance of cilium pathways in endometrium health and animal reproduction. MIR21 and MIR30A would be perfect antagonistic biomarkers for diagnosis of either inflammation or anti-inflammation. These novel findings will set precedent for future genomic studies to aid the dairy industry develop new strategies to reduce endometritis incidence and improve fertility.
Meagan J.STOTTSYangzi ZHANGShuwen ZHANGJennifer J.MICHALJuan VELEZBothe HANSMartin MAQUIVARZhihua JIANG
关键词:ENDOMETRITIS

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