Pseudouridine (5-ribosyluracil) was the first modified ribonucleoside discovered. It is the most abundant natural modified RNA base, and has been deemed the "fifth nucleoside" in RNA. It can be found in structural RNAs, such as transfer, ribosomal and small nuclear RNA. Pseudouridine has been found to enhance base stacking and translation. Pseudouridine-5'-triphosphate (Pseudo-UTP) is used to impart desirable mRNA characteristics such as increased nuclease stability, increased translation or altered interaction of innate immune receptors with in vitro transcribed RNA. Pseudo-UTP, along with 5-methylcytidine-5'-triphosphate (5-methyl-CTP) has shown innate immune suppression in culture and in vivo while enhancing translation in recent publications. For example, Warren et al. determined an efficient means of reprogramming multiple human cell types using modified mRNA that can express the four primary reprogramming proteins. These cells are referred to as induced pluripotency stem cells (iPSCs). Warren et al. found that enzymatically synthesized RNA substituted with Pseudo-UTP, 5-Methyl-CTP and ARCA effectively evaded the cell’s innate immune response, a crucial component in their success. Reduced toxicity due to substitution with Pseudo-UTP, 5-Methyl-CTP was critical since it allowed repeated transfection with in vitro transcribed mRNA over several weeks.
Katalin Karikó, prominent mRNA researcher, references TriLink as a leading manufacturer of Pseudo-UTP; "We value TriLink, it is an excellent company indeed. The product is very good and the customer service is very good too... everybody I know who is making pseudoU RNA is getting it from you."
|Purity||≥97% by AX-HPLC|
|Extinction Coefficient||7,546 Lmol-1cm-1 at 262 nm|
|Molecular Formula||C9H15N2O15P3 (free acid)|
|Molecular Weight||484.10 g/mole (free acid)|
|Recommended Storage||-20°C or below|
|Other Name(s)||Pseudo-UTP, 5-Ribosyl Uracil|
|Application||Aptamers, Epigenetics/DNA Damage, In vitro Transcription, Mutagenesis, Photocrosslinking Studies|
|Nucleotide Category||Base Modified RNA|
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Madore, E.; Florentz, C.; Giegé, R.; Sekine, S.; Yokoyama, S.; Lapointe, J. . Effect of modified nucleotides on Escherichia coli tRNAGlu structure and on its aminoacylation by glutamyl-tRNA synthetase. Predominant and distinct roles of the mnm5 and s2 modifications of U34.
Karikó, Katalin; Muramatsu, Hiromi; Welsh, Frank A.; Ludwig, János; Kato, Hiroki; Akira, Shizuo; Weissman, Drew . Incorporation of pseudouridine into mRNA yields superior nonimmunogenic vector with increased translational capacity and biological stability.
Anderson, Bart R.; Muramatsu, Hiromi; Nallagatla, Subba R.; Bevilacqua, Philip C.; Sansing, Lauren H.; Weissman, Drew; Karikó, Katalin . Incorporation of pseudouridine into mRNA enhances translation by diminishing PKR activation.
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Leppek, K;Byeon, GW;Kladwang, W;Wayment-Steele, HK;Kerr, CH;Xu, AF;Kim, DS;Topkar, VV;Choe, C;Rothschild, D;Tiu, GC;Wellington-Oguri, R;Fujii, K;Sharma, E;Watkins, AM;Nicol, JJ;Romano, J;Tunguz, B;Participants, E;Barna, M;Das, R; . Combinatorial optimization of mRNA structure, stability, and translation for RNA-based therapeutics
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