An essential signaling role for the m3G cap in the transport of U1 snRNP to the nucleus.
The major small nuclear ribonucleoprotein particles (snRNPs) U1, U2, U4 + U6, and U5 have to be transported from the cytoplasm, where they are synthesized, to the nucleus, where they splice pre-messenger RNAs. Since the free core snRNP proteins in the cytoplasm do not enter the nucleus on their own, the nuclear location signal must either reside on the snRNA or be created as a result of snRNA-protein interaction. Here the involvement by the 5'-terminal cap of snRNA molecules in the nucleo-cytoplasmic transport of UsnRNPs has been studied by microinjection of synthetic U1 RNA molecules into frog oocytes; the U1 RNA bore either the normal cap (m3G) or a chemical derivative. Antibodies in the cytoplasm against the m3G cap inhibited the nuclear uptake of U1 snRNP. U1 RNA that was uncapped or contained an unnatural ApppG cap did not enter the nucleus, even though it carried a normal complement of protein molecules. When the ribose ring of the m3G cap was oxidized with periodate, nuclear transport of U1 snRNPs was severely inhibited. Finally, microinjection of m3G cap alone (but not m7G cap) into oocytes severely inhibited the transport of U1 snRNPs to the nucleus. These data suggest that one step in the nuclear uptake of U1 snRNPs involves the m3G cap structure.
Fischer
U
U
Institut für Molekularbiologie und Tumorforschung, Phillipps-Universität Marburg, Federal Republic of Germany.
Lührmann
R
R
D000818:Animals; D001692:Biological Transport; D002467:Cell Nucleus / Q000378:metabolism*; D003593:Cytoplasm / Q000378:metabolism; D005260:Female; D006151:Guanosine / Q000031:analogs & derivatives* / Q000502:physiology; D007700:Kinetics; D009154:Mutation; D009865:Oocytes / Q000648:ultrastructure*; D012315:RNA Caps / Q000502:physiology*; D012261:Ribonucleoproteins / Q000235:genetics / Q000378:metabolism*; D017411:Ribonucleoproteins, Small Nuclear; D015398:Signal Transduction / Q000502:physiology*; D014982:Xenopus laevis
D012315:RNA Caps; D012261:Ribonucleoproteins; D017411:Ribonucleoproteins, Small Nuclear; D006151:Guanosine; C017778:N(2),N(2),7-trimethylguanosine