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Construction Of The Database To Predict The Biological Function Of A-to-I RNA Editing And The Biological Function Research Of The A-to-I RNA

Posted on:2011-04-11Degree:MasterType:Thesis
Country:ChinaCandidate:D L AiFull Text:PDF
GTID:2120360308974965Subject:Biosafety
Abstract/Summary:PDF Full Text Request
RNA editing refers to the processes that alter the primary sequence of a transcript by nucleoside insertion, removal, or modification, and it is the one of the most important events in post-transcriptional gene regulation. There are three types of RNA editing:deletion, insertion and replacement according to the change of base. C-to-U RNA editing in the plants'mitochondria and A-to-I RNA editing in higher eukaryotes are studied extensively recently. In couple of years, A-to-I RNA editing in mammals aroused the concern of scientists. The enzymes responsible for A-to-I editing, the adenosine deaminases acting on RNA (ADARs), are ubiquitously expressed in mammals and specifically recognize partially double-stranded (ds) RNA structures where they modify individual adenosines into inosine. The inosine is identified as G (guanine) in many Biological process, which resulting in the changes in genetic information..Long extended dsRNAs undergo massive editing, whereas RNA duplex structures with bulges and loops are subject to site-selective editing, as observed in several neurotransmitter receptor mRNAs. Since inosine is read as guanosine by the translation machinery, A-to-I editing often leads to codon changes that result in the alteration of protein function. It can also create or destroy pre-mRNA splice signals or lead to alterations in RNA secondary structure.The deficiency or misregulation of A-to-I RNA editing has been implicated in the etiology of neurological diseases, such as epilepsy, amyotrophic lateral sclerosis (ALS), and depression in mammals and it has been shown that a loss of A-to-I editing following the genetic inactivation of ADARs in mammals, as well as flies and the worm, results in behavioral or neurological dysfunctions or embryonic lethality. A-to-I RNA editing generates RNA and protein diversity in higher eukaryotes selectively altering coding and non-coding sequences in nuclear transcripts. These effects include alteration of coding capacity, altered miRNA or siRNA target populations, and altered splicing.Because the A-to-I RNA editing has broad and important biological functions, scientists predict the range of tens of thousands of A-to-I RNA editing sites based on Alu sequences, in the hope of becoming more comprehensive analysis and understanding of the A-to-I RNA editing of biological significance with the large-scale data. Emerging of these large-scale and high-quality data, which subjects to provide favorable conditions for us to study the A-to-I RNA editing. The article is divided into two parts, design and construction of the platfprm to the biological function of A-to-I RNA editing, and the biological function research of the A-to-I RNA editing.Part 1 Design and construction of a platform to predict the biological function of A-to-I RNA editing.Objective:o design and construct a platform application system for A-to-I RNA editing. Method:Analyzed requirements and feasibility of the A-to-I RNA editing.Blueprint of the data structure was designed and accomplished based on the resolution of data flow of A-to-I RNA editing. PHP was used as the background. Perl was the adopted for programming. Performance test and analysis was carried out for A-to-I RNA editing. Results:The platform and the application were finished and applied to analysis the function of A-to-I RNA editing. Conclusion:the system,which can analysis the function of A-to-I RNA editing both in in nucleic acid level and protein level,remarkably increase the efficiency of data management and analysis. The system would have important application significance and have a prosperous future.Part 2 the biological function research of the A-to-I RNA editing.Objective:to explore the biological function of A-to-I RNA editing in translaional level (including the interaction with piRNA, ESE and3'UTR) and transcriptional level (the amino acid change). Methods:using molecular biology techniques to verify the effect on piRNA by A-to-I RNA editing; using the statistics to discuss the impacts on ESE by A-to-I RNA editing. Results:A-to-I RNA editing can change the piRNA sequences, which is probable not universal; 3640 A-to-I RNA editing sites could change the function of ESE; 54.4% of the objective A-to-I RNA editing sites could switch the categories of amino acids. Conclusion:A-to-I RNA editing could take part in broad ofbiological events in nucleic acid level and protein level. The system would have important application significance and have a prosperous future.
Keywords/Search Tags:A-to-I RNA editing, piRNA, ESE
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