In silico study on RNA structures of intronic mutations of beta-globin gene
| Autor: | Nur Imaniati Sumantri, Kenny Lischer, Tomy Abuzairi, Dian Rachma Wijayanti |
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| Rok vydání: | 2020 |
| Předmět: |
0301 basic medicine
Genetics 0303 health sciences Messenger RNA General Immunology and Microbiology In silico Mutant RNA General Medicine Biology General Biochemistry Genetics and Molecular Biology Protein tertiary structure 03 medical and health sciences 030104 developmental biology 0302 clinical medicine Transcription (biology) General Pharmacology Toxicology and Pharmaceutics Nucleic acid structure Gene 030217 neurology & neurosurgery 030304 developmental biology |
| Zdroj: | F1000Research. 9:49 |
| ISSN: | 2046-1402 |
| Popis: | Background: Mutation of the beta-globin gene (HBB) interferes with primary mRNA transcription, leading to beta-thalassemia disease. The IVS1nt1 and IVS1nt5 mutations were reported as two of the most prevalent intronic mutations associated with beta-thalassemia major. These mutations may affect the mRNA structure of the human beta-globin (HBB) gene. However, the mechanism by which variation in HBB alters the mRNA structure remains unclear. The objective of this study was to unveil the secondary and tertiary conformation difference of the mutants compared to the wildtype using in silico analysis. Methods: The sequence of HBB was obtained from Ensemble database and mutated manually at nucleotides 143 (IVS1nt1G>T) and 147 (IVS1nt5G>C). The RNA secondary and tertiary structure were performed by ViennaRNA Web Services and RNA Composer, respectively. Results and Discussion: The results revealed the unique folding characteristics of each mutations for the secondary and tertiary structures. Based on the structure, unwanted folding occurred in the IVS1nt1G>T and IVS1nt5G>C mRNA structures compared to the wild-type structure. This finding was supported by the results of centroid-based analysis and RNA structure analysis, indicating that the larger loops in IVS1nt1 and IVS1nt5 result in an unstable structure. Our study found that intronic mutations affect the mRNA structure of HBB by altering its folding mechanism. |
| Databáze: | OpenAIRE |
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