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Interaction Among Background And The Cis-and Trans-factors Which Can Influence The Alternative Splicing Model Of Human Genetic

Posted on:2011-02-07Degree:DoctorType:Dissertation
Country:ChinaCandidate:W LiuFull Text:PDF
GTID:1100330332982915Subject:Biochemistry and Molecular Biology
Abstract/Summary:PDF Full Text Request
There is a very limited number of genes in human genomic, thirty thousand genes. The large proteomic complexity is achieved by post-transcriptional mechanisms of gene regulation, especially by the network of alternative splicing.The classic study of alternative splicing focused on selecting cis- and trans- factors. Our points in this paper are focused on the two below1. The strength of the cis-elements is not only decided by the sequences of the elements but also interfered by the position and background it located2. mRNA can form secondary structure in vivo, and regulate the function of the cis-element near it.Over 90% of human gene was alternative spliced. In classic theory, pre-mRNA was transcribed and package with the hnRNPs to forced to be linear. Then the cis-elements on the mRNA were bound by the trans-factors and the components of splicesome were recruited to the splicing site and splice began. The strength of elements is context-independent, only related to the sequence of the elements itself.Recently, more and more examples implied that the independence of the elements is rather limited. Elements interact with the background they located in a very precise way. In some cases, these interaction is so strong that element functioned in a rather different way on different positions. But till now, there is no systemic study on this positional effect. Data about this phenomena is both complex and puzzled.Here we divided the phenomena into three parts, and studied them respectively.Firstly, we found out the splicing signals (including all elements) worked in a clustered way. When located apart from other elements, the element tends to show no function. Functional position of different elements is diverse, but they all tend to clustered near the splicing site.Secondly, when there are two competitive 5'splicing site, the stronger one will be chosen. But sometimes the distance between the splicing site and other splicing signals may be more important than the strength of the splicing site.Thirdly, secondary structure on the pre-mRNA play an important role in the function of the element near it or inside it.
Keywords/Search Tags:alternative splicing, positional effect, secondary structure
PDF Full Text Request
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