I post this question twice, please don\'t answer this post if you already answer
ID: 189120 • Letter: I
Question
I post this question twice, please don't answer this post if you already answer the other one, if you can answer different answer that's fine. REASON WHY I POST IT TWICE, I NEED TWO DIFFERENT VIEW.
Discussion
Hi All - this week you will learn about DNA - the molecule of life! You may think that protein-coding genes are the most important, but results from the Human Genome Project revealed that only about 2% of our DNA codes for protein - so what about the rest of the "junk DNA" (or non-protein coding portion of the genome) - is it functionally important? Yes! Scientists are learning how "the non-protein-coding portion of the genome is of crucial functional importance: for normal development and physiology and for disease". I would like you to please choose a topic with regards to the non-protein coding portion of the genome (this will introduce you to gene regulation which we will cover in chapter 11) or you may also choose to write about a topic that describes a mutation in any protein that is involved in DNA replication, transcription, or translation (we did not talk about all of the enzymes involved in those processes). Please list your reputable source - this is worth 0.5 pt (even if you use one of my sources below) and tell me WHY you chose your topic (this is worth 1 pt.) please try to briefly explain your topic to the best of your knowledge - I don't expect you to write a lot of detail about your topic - it might be hard to understand (which you are welcome to comment on in your paragraph)!
Examples to choose from (but not limited to) include: noncoding RNAs (snRNAs, miRNAs, siRNAs, snoRNAs, piRNAs, lincRNAs) and RNA therapeutics:
LIST:
1. http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4119351/ (Development of microRNA therapeutics is coming of age)
2. http://www.umassmed.edu/rti/ (RNA Therapeutics Institute)
3. http://www.genengnews.com/insight-and-intelligence/rna-based-therapeutics-and-vaccines/77900520/
4. http://genesdev.cshlp.org/content/26/21/2361.full (Biology of PIWI-Interacting RNAs: new insights into biogenesis and function inside and outside of germlines)
5. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4265212/ (PIWI proteins and their interactors in piRNA biogenesis, germline development and gene expression)
6. http://www.news-medical.net/news/20121203/microRNAs-play-an-important-role-during-embryonic-development.aspx
7. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4578617/ (the role of microRNAs in cell fate determination)
8. http://news.berkeley.edu/2017/01/13/scientists-reprogram-embryonic-stem-cells-to-expand-their-potential/
9. http://www.the-scientist.com/?articles.view/articleNo/40871/title/The-Second-Coming-of-RNAi/
10. http://web.mit.edu/newsoffice/2013/cardiac-development-needs-more-than-protein-coding-genes-0124.html (long non-coding RNA molecules)
11. http://www.alzforum.org/news/research-news/new-role-micrornas-torpedoes-sink-neurons(microRNAs)
12. http://ghr.nlm.nih.gov/condition/rothmund-thomson-syndrome (mutation in human helicase gene)
13. http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3633371/ (mutation in mitochondrial helicase gene called TWINKLE)
14. http://sfari.org/news-and-opinion/news/2013/in-autism-related-disorders-rna-turns-out-to-be-key (RNA topoisomerase)
15. http://ghr.nlm.nih.gov/gene/TERC (dyskeratosis congenita - mutations in the TERC gene - the RNA component of telomerase)
16. http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3853347/ (Top3beta is an RNA topoisomerase that works with Fragile X syndrome protein to promote synapse formation)
The following 3 articles discuss long non-coding RNAs - there are many examples in each article so you only need to talk about one example - not the whole article:
1. http://www.sciencedirect.com/science/article/pii/S2468054016300063 (mechanism of action and functional utility)
2. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5084630/ (dysregulated expression in ovarian cancer)
3. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4736767/ (stem cells)
Explanation / Answer
The topic I choose is the one related with the development of microRNA therapeutics which from my point of view are crucial for some biological processes.
MicroRNAs represent a class of small (18 to 28 nucleotide-long) noncoding RNA molecules. These molecules either degrade protein-coding transcripts or inhibit their translation into proteins. A very important point which I am very interested in microRNAs is because since their discovery the main dogma of molecular biology that mentions DNA is transcribed into RNA has changed.
From all mentioned before, microRNAs have emerged as a promising targets for therapeutic treatment. This is the central objective of the review “Development of microRNA therapeutic coming of age”. They describe what are the more important strategies for therapeutic modulation of microRNA activity in vivo, also how some specific microRNAs have been used for treatment of cancer, cardiovascular disease, diabetes and HCV infection.
The two approaches that are employed to modulate microRNA activity are: a) restoring the function of a microRNA using either synthetic double-stranded microRNA or viral vector-based overexpression and b) inhibiting the function of a microRNA using chemically modified antimir oligonucleotides. Their promising used is undeniable but one of the main challenge to use microRNA as treatment is the delivery step which needs to consider the efficiency and safety delivery. For that reason there are two options in therapy in vivo: a) formulated, synthetic, double stranded microRNA mimics, b)viral constructs over-expressing the lost or down-regulated microRNA.
Some studies have shown that microRNA are related in human diseases because they are frequently deregulated. This has suggest that microRNA could work as viable targets for the development of microRNA treatments. Some examples mentioned during the review are: a)miR-34 based cancer therapeutics which can be replaced lost or down-regulated microRNAs in cancer cells; b) miR-33 for treatment of atherosclerosis some reports have shown that two genes harbor two intronic microRNAs, which regulate cholesterol. Studies suggests that silencing of miR-33 could be a useful therapeutic strategy for atherosclerosis; c) miR-208 for the treatment of heart failure and diabetes, the most important genes for determining cardiomyocyte contractility is the alpha-myosin heavy chain which produces a microRNA, known as miR-208 which can be inhibited with anti-miR-208: d) miR-122 for the treatment of HCV infection, miR-122 is a liver-expressed microRNA that is implicated in the regulation of hepatic cholesterol, lipid and iron metabolism. The inhibition using an antimiR results in the decreased of microRNAs in the liver and reducing the levels of cholesterol.
Of course, there are still a long journey to see these benefits from microRNAs in our daily life as a therapeutic treatment. For now, the antimir-122 for treatment of HCV infection is in phase 2 study, which is a light that in future we can see these types of treatment in clinical medicine.