共查询到19条相似文献,搜索用时 78 毫秒
1.
2.
真核基因可变剪接研究现状与展望 总被引:2,自引:0,他引:2
mRNA前体(pre-mRNA)的可变剪接是控制基因表达和产生蛋白质多样性的重要机制,是功能基因组时代的研究重点之一。生物信息学在识别可变剪接基因及其结构、分析可变剪接的功能和调控方式等方面具有重要作用。除了耗时的实验研究,识别可变剪接基因及其结构主要通过EST、mRNA等转录数据与基因组序列进行比对,获得同一基因的不同结构方式。分析蛋白质产物可对可变剪接的功能进行预测;潜在调控元件的统计分析则可为可变剪接调控机制的研究提供必要的数据。转录数据的时空信息以及比较基因组学对理解可变剪接信息的精确调控将提供重要资料。可变剪接及其调控机制的深入研究将为基因组和蛋白质组之间的对接提供重要的桥梁。 相似文献
3.
《中国科学:生命科学》2015,(12)
可变剪接是造成生物体内转录组和蛋白质组多样性和复杂性的重要机制.自20世纪80年代间被首次报道以来,人们逐渐意识到生物体内的可变剪接现象广泛存在,其能够调节增殖、分化、发育、凋亡等一系列重要的生物学进程,且机体对其调控有着高度的精密性和统一性.近年来,随着高通量测序技术及生物信息学方法的飞速发展和完善,可变剪接研究领域取得了一系列新的成就,人们对可变剪接的认识也在不断加深,从最初对单一可变剪接事件的研究逐步深入到组学层面的分析:高通量组学数据的不断产出、整合,使得大规模、系统性可变剪接亚型功能的研究成为可能;在更为宏观的领域,组织、器官、物种或生理病理状态下特异性的剪接模式也逐渐为人们所知晓;同时,借助组学手段,剪接层面的临床治疗策略也开始崭露头角,并且有着传统分子治疗无可比拟的优越性.本文从组学的角度出发,回顾了近年来可变剪接领域取得的最新进展,并对其未来在基础及应用领域的发展方向做了初步的展望. 相似文献
4.
5.
目的:利用RT-PCR技术验证并确认基于小鼠外显子芯片发现的部分缺血相关基因的表达,以鉴定候选基因的外显子是否发生可变剪接,从而实现对外显子芯片结果的鉴定。方法:根据生物信息学分析结果,选取小鼠外显子芯片中的3个基因(Ube3c,6330439K17Rik,Atp7a),在预测发生可变剪接的外显子两侧设计上下游引物,PCR后进行凝胶回收,再克隆到载体中进行测序。结果:RT-PCR及测序结果表明,Ube3c基因在6号外显子、6330439K17Rik基因在12号外显子、Atp7a基因在3号外显子发生可变剪接,与芯片预测结果一致。结论:RT-PCR技术可针对外显子芯片的结果进行可靠性验证,为可变剪接基因表达研究提供了一种有效手段。 相似文献
6.
《生物物理学报》2015,(1)
研究可变剪接和蛋白质结构多样性之间的相关性,对于理解可变剪接的功能具有重要意义。已有研究支持可变剪接增加蛋白质结构多样性的观点,但可变剪接影响蛋白质结构的程度、机制等还尚未阐明。作者基于具有确定三维结构的可变剪接蛋白质变体数据,从蛋白质结构差异和结构稳定性两个方面对致病和非致病的可变剪接蛋白质变体对进行了比较分析;通过建立实际可变剪接变体集和随机可变剪接变体集,并定义蛋白质的多样性增量(increment of diversity,ID)和疏水非均一性(hydrophobic non-uniformity,HI),研究了可变剪接发生的非随机性。结果表明:现有的多数可变剪接事件与随机剪接相比,倾向于增加蛋白质结构多样性;产生结构差异较大蛋白质的可变剪接事件倾向于导致疾病的发生。作者还提出了正负选择压力的动态平衡假说解释这一现象,认为与生命活动相联系的正选择压力促使增加蛋白质结构多样性的可变剪接事件在群体中固定,但反向的负选择压力约束着可变剪接改变蛋白质结构的尺度,细胞中现有的可变剪接正是这两种正负选择压力之间保持动态平衡的结果。 相似文献
7.
完整基因结构的预测是当前生命科学研究的一个重要基础课题,其中一个关键环节是剪接位点和各种可变剪接事件的精确识别.基于转录组测序(RNA-seq)数据,识别剪接位点和可变剪接事件是近几年随着新一代测序技术发展起来的新技术策略和方法.本工作基于黑腹果蝇睾丸RNA-seq数据,使用TopHat软件成功识别出39718个果蝇剪接位点,其中有10584个新剪接位点.同时,基于剪接位点的不同组合,针对各类型可变剪接特征开发出计算识别算法,成功识别了8477个可变剪接事件(其中新识别的可变剪接事件3922个),包括可变供体位点、可变受体位点、内含子保留和外显子缺失4种类型.RT-PCR实验验证了2个果蝇基因上新识别的可变剪接事件,发现了全新的剪接异构体.进一步表明,RNA-seq数据可有效应用于识别剪接位点和可变剪接事件,为深入揭示剪接机制及可变剪接生物学功能提供新思路和新手段. 相似文献
8.
9.
目的:研究基因Srrm1/SRm160的可变剪接。方法:应用RT-PCR研究Srrm1/SRm160的可变剪接,通过蛋白质的翻译抑制和RNA干扰研究剪接异构体是否经历无义突变介导的mRNA降解(NMD)过程。结果:获得Srrm1/SRm160新的可变剪接异构体,该异构体产生提前终止密码子,翻译抑制和RNA干扰证实含有提前终止密码子的剪接体经过NMD而降解。结论:Srrm1/SRm160通过可变剪接和NMD调节自身的表达水平,作为剪接因子进一步调节其他基因的可变剪接。 相似文献
10.
黑曲霉Aspergillus niger因能够产生大量的木质纤维素降解酶而在木质纤维素资源利用中发挥重要作用。目前,有关黑曲霉基因组中与木质纤维素降解相关的基因是否存在可变剪接的情况尚不清楚。本研究以黑曲霉CBS513.88菌株为研究对象,采用rMATS和ABLas两种方法对黑曲霉在葡萄糖为唯一碳源(G组)和小麦秸秆为唯一碳源(WS组)下的56个木质纤维素降解酶基因的可变剪接事件进行分析,并通过RT-PCR扩增和内含子特异性扩增对3个典型基因的可变剪接体进行了验证。结果表明,ABLas可变剪接分析算法相较于rMATS分析算法更为准确,ABLas分析算法显示G组和WS组共有21个木质纤维素降解酶基因出现了可变剪接,可变剪接类型以内含子保留(IR)为主,占所有可变剪接事件的82.85%。另外,G组和WS组发生可变剪接的木质纤维素降解酶基因也有所不同:G组发生可变剪接的基因为13个,WS组发生可变剪接的基因为14个,两组都发生可变剪接的基因为6个,这表明黑曲霉木质纤维素降解酶基因的可变剪接在不同生长条件下存在差异,另一方面,黑曲霉中众多可变剪接体的存在也为开发新型的木质纤维素降解酶资源提供基础。 相似文献
11.
Bioinformatics analysis of alternative splicing 总被引:5,自引:0,他引:5
Over the past few years, the analysis of alternative splicing using bioinformatics has emerged as an important new field, and has significantly changed our view of genome function. One exciting front has been the analysis of microarray data to measure alternative splicing genome-wide. Pioneering studies of both human and mouse data have produced algorithms for discerning evidence of alternative splicing and clustering genes and samples by their alternative splicing patterns. Moreover, these data indicate the presence of alternative splice forms in up to 80 per cent of human genes. Comparative genomics studies in both mammals and insects have demonstrated that alternative splicing can in some cases be predicted directly from comparisons of genome sequences, based on heightened sequence conservation and exon length. Such studies have also provided new insights into the connection between alternative splicing and a variety of evolutionary processes such as Alu-based exonisation, exon creation and loss. A number of groups have used a combination of bioinformatics, comparative genomics and experimental validation to identify new motifs for splice regulatory factors, analyse the balance of factors that regulate alternative splicing, and propose a new mechanism for regulation based on the interaction of alternative splicing and nonsense-mediated decay. Bioinformatics studies of the functional impact of alternative splicing have revealed a wide range of regulatory mechanisms, from NAGNAG sites that add a single amino acid; to short peptide segments that can play surprisingly complex roles in switching protein conformation and function (as in the Piccolo C2A domain); to events that entirely remove a specific protein interaction domain or membrane anchoring domain. Common to many bioinformatics studies is a new emphasis on graph representations of alternative splicing structures, which have many advantages for analysis. 相似文献
12.
13.
14.
15.
Alternative splicing and evolution 总被引:16,自引:0,他引:16
Boue S Letunic I Bork P 《BioEssays : news and reviews in molecular, cellular and developmental biology》2003,25(11):1031-1034
16.
Kirschbaum-Slager N Lopes GM Galante PA Riggins GJ de Souza SJ 《Genetics and molecular research : GMR》2004,3(4):512-520
Although alternative splicing of many genes has been found associated with different stages of tumorigenesis and splicing variants have been characterized as tumor markers, it is still not known whether these examples are sporadic or whether there is a broader association between the two phenomena. In this report we evaluated, through a bioinformatics approach, the expression of splicing factors in both normal and tumor tissues. This was possible by integrating data produced by proteomics, serial analysis of gene expression (SAGE) and microarray experiments. We observed a significant shift in the expression of splicing factors in tumors in both SAGE and microarray data, resulting from a large amount of experiments. We discuss that this supports the notion of a broader association between alternative splicing and cell transformation, and that splicing factors may be involved in oncogenic pathways. 相似文献
17.
Alternative splicing is a crucial mechanism by which diverse gene products can be generated from a limited number of genes, and is thought to be involved in complex orchestration of eukaryotic gene expression. Next-generation sequencing technologies, with reduced time and cost, provide unprecedented opportunities for deep interrogation of alternative splicing at the genome-wide scale. In this study, an integrated software SplicingViewer has been developed for unambiguous detection, annotation and visualization of splice junctions and alternative splicing events from RNA-Seq data. Specifically, it allows easy identification and characterization of splice junctions, and holds a versatile computational pipeline for in-depth annotation and classification of alternative splicing with different patterns. Moreover, it provides a user-friendly environment in which an alternative splicing landscape can be displayed in a straightforward and flexible manner. In conclusion, SplicingViewer can be widely used for studying alternative splicing easily and efficiently. SplicingViewer can be freely accessed at http://bioinformatics.zj.cn/splicingviewer. 相似文献
18.