Towards novel efficient and stable nuclear import signals: synthesis and properities of trimethylguanosine cap analogs modified within the 5’, 5’ –triphosphate bridge
PBN-AR
Instytucja
Instytut Fizyki Polskiej Akademii Nauk
Informacje podstawowe
Główny język publikacji
en
Czasopismo
ORGANIC & BIOMOLECULAR CHEMISTRY
ISSN
1477-0520
EISSN
1477-0539
Wydawca
ROYAL SOC CHEMISTRY
DOI
URL
Rok publikacji
2014
Numer zeszytu
45
Strony od-do
9184-9199
Numer tomu
12
Link do pełnego tekstu
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Słowa kluczowe
en
MESSENGER-RNA STRUCTURAL BASIS DECAPPING ENZYME SMALL NUCLEOLAR TRANSLATIONAL-EFFICIENCY CHEMICAL-SYNTHESIS BINDING PROTEIN U1 SNRNA STABILITY EIF4E
Streszczenia
Język
en
Treść
A trimethylguanosine (TMG) cap is present at the 5' end of several small nuclear and nucleolar RNAs. Recently, it has been reported that the TMG cap is a potential nuclear import signal for nucleus-targeting therapeutic nucleic acids and proteins. The import is mediated by recognition of the TMG cap by the snRNA transporting protein, snurportin1. This work describes the synthesis and properties of a series of dinucleotide TMG cap (m3 2,2,7GpppG) analogs modified in the 5', 5'-triphosphate bridge as tools to study TMG cap-dependent biological processes. The bridge was altered at different positions by introducing either bridging (imidodiphosphate, O to NH and methylenebisphosphonate, O to CH2) or non-bridging (phosphorothioate, O to S and boranophosphate, O to BH3) modifications, or by elongation to tetraphosphate. The stability of novel analogs in blood serum was studied to reveal that the alpha,beta-bridging O to NH substitution (m(3)(2,2,7)GppNHpG) confers the highest resistance. Short RNAs capped with analogs containing a, A-bridging (m(3)(2,2,7)GppNHpG) or beta-non-bridging (m(3)(2,2,7)GppSpG D2) modifications were resistant to decapping pyrophosphatase, hNudt16. Preliminary studies on binding by human snurportin1 revealed that both O to NH and O to S substitutions support this binding. Due to favorable properties in all three assays, m(3)(2,2,7)GppNHpG was selected as a promising candidate for further studies on the efficiency of the TMG cap as a nuclear import signal.
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Oryginalny artykuł naukowy przedstawia rezultaty oryginalnych badań naukowych lub eksperymentu.
Original article
Original article presents the results of original research or experiment.
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System-identifier
PBN-R:540628
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