Chapter title |
Specific Increase of Protein Levels by Enhancing Translation Using Antisense Oligonucleotides Targeting Upstream Open Frames
|
---|---|
Chapter number | 9 |
Book title |
RNA Activation
|
Published in |
Advances in experimental medicine and biology, June 2017
|
DOI | 10.1007/978-981-10-4310-9_9 |
Pubmed ID | |
Book ISBNs |
978-9-81-104309-3, 978-9-81-104310-9
|
Authors |
Xue-Hai Liang, Wen Shen, Stanley T. Crooke, Liang, Xue-Hai, Shen, Wen, Crooke, Stanley T. |
Editors |
Long-Cheng Li |
Abstract |
A number of diseases are caused by low levels of key proteins; therefore, increasing the amount of specific proteins in human bodies is of therapeutic interest. Protein expression is downregulated by some structural or sequence elements present in the 5' UTR of mRNAs, such as upstream open reading frames (uORF). Translation initiation from uORF(s) reduces translation from the downstream primary ORF encoding the main protein product in the same mRNA, leading to a less efficient protein expression. Therefore, it is possible to use antisense oligonucleotides (ASOs) to specifically inhibit translation of the uORF by base-pairing with the uAUG region of the mRNA, redirecting translation machinery to initiate from the primary AUG site. Here we review the recent findings that translation of specific mRNAs can be enhanced using ASOs targeting uORF regions. Appropriately designed and optimized ASOs are highly specific, and they act in a sequence- and position-dependent manner, with very minor off-target effects. Protein levels can be increased using this approach in different types of human and mouse cells, and, importantly, also in mice. Since uORFs are present in around half of human mRNAs, the uORF-targeting ASOs may thus have valuable potential as research tools and as therapeutics to increase the levels of proteins for a variety of genes. |
Mendeley readers
Geographical breakdown
Country | Count | As % |
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Unknown | 27 | 100% |
Demographic breakdown
Readers by professional status | Count | As % |
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Researcher | 8 | 30% |
Other | 5 | 19% |
Student > Ph. D. Student | 5 | 19% |
Student > Bachelor | 2 | 7% |
Professor | 1 | 4% |
Other | 2 | 7% |
Unknown | 4 | 15% |
Readers by discipline | Count | As % |
---|---|---|
Biochemistry, Genetics and Molecular Biology | 10 | 37% |
Agricultural and Biological Sciences | 7 | 26% |
Pharmacology, Toxicology and Pharmaceutical Science | 2 | 7% |
Medicine and Dentistry | 1 | 4% |
Engineering | 1 | 4% |
Other | 0 | 0% |
Unknown | 6 | 22% |