Towards novel efficient and stable nuclear import signals: synthesis and properties of trimethylguanosine cap analogs modified within the 5',5'-triphosphate bridge.

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.

Synthesis and evaluation of stability of m3G-CAP analogues in serum-supplemented medium and cytosolic extract.

Increased efficiency in splice-correction (splice-switching) has been shown by use of a synthetic RNA 5'-end nuclear localization signal composed of an m3G-CAP. Use of the m3G-CAP as an NLS signal for therapeutic compounds in vivo is likely to require additional stability towards enzymatic degradation. For this reason introduction of stabilizing modifications into the triphosphate bridge may be beneficial.