GCD 3022 1st Edition Lecture 25 Outline of Last Lecture I RNA interference a Definition b Process II Genetic Imprinting a Igf2 gene b ICR mutation III mRNA degradation a mRNA half life b advantages and disadvantages of short half life c advantages and disadvantages of long half life IV Alternative splicing a Example b Explanation Outline of Current Lecture I Epigenetics a Epigenetics vs classical genetics b Epigenetic gene regulation c Targeted genes These notes represent a detailed interpretation of the professor s lecture GradeBuddy is best used as a supplement to your own notes not as a substitute d Igf2 gene II Splicing Regulation a SR proteins b Advantage of alternative splicing c Splicing repressor Example 1 d Splicing repressor Example 2 e Types of exons III mRNA half life a Definition b AU rich elements IV RNA interference a Mechanism b Non coding RNA c miRNA hybridization d RNAs in RNA interference Current Lecture I Epigenetics a Epigenetics vs classical genetics i Epigenetics is the study of changes in gene expression that occur via different methods than classical genetics The big difference between epigenetics and classical genetics is that the changes in gene expression in epigenetics are reversible and do not change the DNA sequence b Epigenetic gene regulation the processes that underlie epigenetic gene regulation are DNA methylation covalent histone modifications chromatin remodeling and histone variants c Targeted genes a gene can be targeted for epigenetic regulation via the binding of a transcription factor or non coding RNA d Igf2 gene the Igf2 gene follows a cis pattern of epigenetic regulation which means that the activation of the gene is not passed on to other copies of the gene The ICR and DMR sequences are the methylated sequences in the Igf2 gene and these sequences are only methylated in spermatogenesis male only This results in the binding of CTC factors to the unmethylated ICR and DMR regions on the female s gene which inactivates the Igf2 gene II Splicing Regulation a SR proteins common splicing regulators b Advantages of alternative splicing one primary transcript can give rise to several different mRNAs one primary transcript can give rise to several different proteins and it allows cells to produce different versions of one protein that serve different but related functions c Splicing repressor Example 1 a pre mRNA has 5 exons and a splicing repressor blocks the activity on the 3 splice site of intron 3 Therefore exons 1 2 3 and 5 would be present in the mature mRNA and exon 5 would be skipped d Splicing repressor Example 2 another pre mRNA contains 5 exons but the splicing repressor binds to the 5 splice site of intron 3 This means that the mature mRNA would contain exons 1 2 3 4 and 5 as well as intron 3 because the splicing repressor missed the repressed splice site e Types of exons the two types of exons are constitutive always present in mRNA and alternative not always present in mRNA III mRNA half life a Definition the time it takes for the starting amount of mRNA to decrease by half b AU rich elements bind in the 3 non coding region of the mRNA and contribute to determining mRNA half life IV RNA interference a Mechanism transcription of micro RNA occurs in the nucleus The miRNA is then folded into a hairpin loop and transported into the cytoplasm Either pre miRNA or pre siRNA are cut into a short segment by a dicer and become mature mi or siRNA This miRNA or siRNA binds to a protein complex RISC complex One of the miRNA or siRNA strands degrades and the other associates with the target mRNA through complementary base pairing The mRNA then either degrades or is silenced b Non coding RNA an RNA molecule that does not code for a protein c miRNA hybridization the reason that miRNA binds to a specific mRNA is because it hybridizes with the mRNA that is its complement d RNAs in RNA interference these RNAs are encoded by the genome encoded by viruses or synthesized by researchers
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