SNURPORTIN1, AN M(3)G-CAP-SPECIFIC NUCLEAR IMPORT RECEPTOR WITH A NOVEL DOMAIN-STRUCTURE

The nuclear import of the spliceosomal snRNPs U1, U2, U4 and U5, is de pendent on the presence of a complex nuclear localization signal (NLS) . The latter is composed of the 5'-2,2,7-terminal trimethylguanosine ( m(3)G) cap structure of the U snRNA and the Sm core domain. Here, we d escribe the isolation and cDNA cloning of a 45 kDa protein, termed snu rportin1, which interacts specifically with m(3)G-cap but not m(7)G-ca p structures. Snurportin1 enhances the m(3)G-cap-dependent nuclear imp ort of U snRNPs in both Xenopus laevis oocytes and digitonin-permeabil ized HeLa cells, demonstrating that it functions as an snRNP-specific nuclear import receptor. Interestingly, solely the m(3)G-cap and not t he Sm core NLS appears to be recognized by snurportin1, indicating tha t at least two distinct import receptors interact with the complex snR NP NLS. Snurportin1 represents a novel nuclear import receptor which c ontains an N-terminal importin beta binding (IBB) domain, essential fo r function, and a C-terminal m(3)G-cap-binding region with no structur al similarity to the arm repeat domain of importin alpha.