3-(3-Amino-3-carboxypropyl)uridine, an indispensable compound extensively applied in biomedical research and pharmaceutical advancement, assumes a pivotal function in the amalgamation of nucleic acids and RNA alteration. Its multifaceted attributes make it an invaluable tool for unraveling the intricate intricacies of RNA's structure, function, and the impact of selective modifications on a diverse array of ailments, encompassing cancer and neurodegenerative disorders.
Reference Reading
1. Metabolomic changes in cats with renal disease and calcium oxalate uroliths
Dennis E Jewell, Selena K Tavener, Regina L Hollar, Kiran S Panickar. Metabolomics. 2022 Aug 13;18(8):68. doi: 10.1007/s11306-022-01925-4.
There is a significant incidence of cats with renal disease (RD) and calcium oxalate (CaOx) kidney uroliths in domesticated cats. Foods which aid in the management of these diseases may be enhanced through understanding the underlying metabolomic changes. Assess the metabolomic profile with a view to identifying metabolomic targets which could aid in the management of renal disease and CaOx uroliths. This is a retrospective investigation of 42 cats: 19 healthy kidney controls, 11 with RD, and 12 that formed CaOx nephroliths. Cats were evaluated as adults (2 through 7 years) and at the end of life for plasma metabolomics, body composition, and markers of renal dysfunction. Kidney sections were assessed by Pizzolato stain at the end of life for detection of CaOx crystals. CaOx stone presence was also assessed by analysis of stones removed from the kidney at the end of life. There were 791 metabolites identified with 91 having significant (p < 0.05, q < 0.1) changes between groups. Many changes in metabolite concentrations could be explained by the loss of renal function being most acute in the cats with RD while the cats with CaOx stones were intermediate between control and RD (e.g., urea, creatinine, pseudouridine, dimethylarginines). However, the concentrations of some metabolites differentiated RD from CaOx stone forming cats. These were either increased in the RD cats (e.g., cystathionine, dodecanedioate, 3-(3-amino-3-carboxypropyl) uridine, 5-methyl-2'-deoxycytidine) or comparatively increased in the CaOx stone forming cats (phenylpyruvate, 4-hydroxyphenylpyruvate, alpha-ketobutyrate, retinal). The metabolomic changes show specific metabolites which respond generally to both renal diseases while the metabolomic profile still differentiates cats with RD and cats with CaOx uroliths.
2. Biogenesis and functions of aminocarboxypropyluridine in tRNA
Mayuko Takakura, Kensuke Ishiguro, Shinichiro Akichika, Kenjyo Miyauchi, Tsutomu Suzuki. Nat Commun. 2019 Dec 5;10(1):5542. doi: 10.1038/s41467-019-13525-3.
Transfer (t)RNAs contain a wide variety of post-transcriptional modifications, which play critical roles in tRNA stability and functions. 3-(3-amino-3-carboxypropyl)uridine (acp3U) is a highly conserved modification found in variable- and D-loops of tRNAs. Biogenesis and functions of acp3U have not been extensively investigated. Using a reverse-genetic approach supported by comparative genomics, we find here that the Escherichia coli yfiP gene, which we rename tapT (tRNA aminocarboxypropyltransferase), is responsible for acp3U formation in tRNA. Recombinant TapT synthesizes acp3U at position 47 of tRNAs in the presence of S-adenosylmethionine. Biochemical experiments reveal that acp3U47 confers thermal stability on tRNA. Curiously, the ΔtapT strain exhibits genome instability under continuous heat stress. We also find that the human homologs of tapT, DTWD1 and DTWD2, are responsible for acp3U formation at positions 20 and 20a of tRNAs, respectively. Double knockout cells of DTWD1 and DTWD2 exhibit growth retardation, indicating that acp3U is physiologically important in mammals.
3. Amine-to-Azide Conversion on Native RNA via Metal-Free Diazotransfer Opens New Avenues for RNA Manipulations
Olga A Krasheninina, Julia Thaler, Matthias D Erlacher, Ronald Micura. Angew Chem Int Ed Engl. 2021 Mar 22;60(13):6970-6974. doi: 10.1002/anie.202015034.
A major challenge in the field of RNA chemistry is the identification of selective and quantitative conversion reactions on RNA that can be used for tagging and any other RNA tool development. Here, we introduce metal-free diazotransfer on native RNA containing an aliphatic primary amino group using the diazotizing reagent fluorosulfuryl azide (FSO2 N3 ). The reaction provides the corresponding azide-modified RNA in nearly quantitatively yields without affecting the nucleobase amino groups. The obtained azido-RNA can then be further processed utilizing well-established bioortho-gonal reactions, such as azide-alkyne cycloadditions (Click) or Staudinger ligations. We exemplify the robustness of this approach for the synthesis of peptidyl-tRNA mimics and for the pull-down of 3-(3-amino-3-carboxypropyl)uridine (acp3 U)- and lysidine (k2 C)-containing tRNAs of an Escherichia coli tRNA pool isolated from cellular extracts. Our approach therefore adds a new dimension to the targeted chemical manipulation of diverse RNA species.
