Duchenne muscular dystrophy (DMD) is an X-linked recessive genetic disease caused by mutations in the gene that encodes dystrophin, a large protein that plays an important role in the development of normal muscle fibers. The Dystrophin gene is immense, spanning 2.5 million base pairs, and includes 79 exons and 78 introns. Many of the mutations that cause DMD produce premature stop codons, which bring protein synthesis to a halt, resulting in a greatly shortened and nonfunctional form of dystrophin. Some geneticists have proposed treating DMD patients by introducing small RNA molecules that cause the spliceosome to skip the exon containing the stop codon (A. Goyenvalle et al., 2004. Science 306:1796–1799). The introduction of the small RNAs will produce a protein that is somewhat shortened because an exon is skipped and some amino acids are missing, but it may still result in a protein that has some function. The small RNAs, antisense RNAs, used for exon skipping are complementary to bases in the pre- mRNA, which will prevent proper associating of spliceosome for intron removal. Knowing this information, and based on what you learned about splicing, where on the pre-mRNA should be the targets of these antisense RNA? You need to be specific regarding whether the target sequences are upstream, downstream, and whether is located on the 5’ or 3’ end of the mutated exon or introns. You may use the Figure below as reference. Provide a rationale for your purpose targets. A brief explanation of how anti sense RNAs work may be helpful to support your arguments.
Duchenne muscular dystrophy (DMD) is an X-linked recessive genetic disease caused by mutations in the gene that encodes dystrophin, a large protein that plays an important role in the development of normal muscle fibers. The Dystrophin gene is immense, spanning 2.5 million base pairs, and includes 79 exons and 78 introns. Many of the mutations that cause DMD produce premature stop codons, which bring protein synthesis to a halt, resulting in a greatly shortened and nonfunctional form of dystrophin.
Some geneticists have proposed treating DMD patients by introducing small RNA molecules that cause the spliceosome to skip the exon containing the stop codon (A. Goyenvalle et al., 2004. Science 306:1796–1799). The introduction of the small RNAs will produce a protein that is somewhat shortened because an exon is skipped and some amino acids are missing, but it may still result in a protein that has some function.
The small RNAs, antisense RNAs, used for exon skipping are complementary to bases in the pre- mRNA, which will prevent proper associating of spliceosome for intron removal. Knowing this information, and based on what you learned about splicing, where on the pre-mRNA should be the targets of these antisense RNA? You need to be specific regarding whether the target sequences are upstream, downstream, and whether is located on the 5’ or 3’ end of the mutated exon or introns. You may use the Figure below as reference. Provide a rationale for your purpose targets. A brief explanation of how anti sense RNAs work may be helpful to support your arguments.
Trending now
This is a popular solution!
Step by step
Solved in 3 steps
