SMN, the spinal muscular atrophy protein, forms a pre-import snRNP complex with snurportin1 and importin beta.
The survival of motor neuron (SMN) protein is mutated in patients with spinal muscular atrophy (SMA). SMN is part of a multiprotein complex required for biogenesis of the Sm class of small nuclear ribonucleoproteins (snRNPs). Following assembly of the Sm core domain, snRNPs are transported to the nucleus via importin beta. Sm snRNPs contain a nuclear localization signal (NLS) consisting of a 2,2,7-trimethylguanosine (TMG) cap and the Sm core. Snurportin1 (SPN) is the adaptor protein that recognizes both the TMG cap and importin beta. Here, we report that a mutant SPN construct lacking the importin beta binding domain (IBB), but containing an intact TMG cap-binding domain, localizes primarily to the nucleus, whereas full-length SPN localizes to the cytoplasm. The nuclear localization of the mutant SPN was not a result of passive diffusion through the nuclear pores. Importantly, we found that SPN interacts with SMN, Gemin3, Sm snRNPs and importin beta. In the presence of ribonucleases, the interactions with SMN and Sm proteins were abolished, indicating that snRNAs mediate this interplay. Cell fractionation studies showed that SPN binds preferentially to cytoplasmic SMN complexes. Notably, we found that SMN directly interacts with importin beta in a GST-pulldown assay, suggesting that the SMN complex might represent the Sm core NLS receptor predicted by previous studies. Therefore, we conclude that, following Sm protein assembly, the SMN complex persists until the final stages of cytoplasmic snRNP maturation and may provide somatic cell RNPs with an alternative NLS.
Pubmed ID: 12095920
- Narayanan U
- Ospina JK
- Frey MR
- Hebert MD
- Matera AG
Human molecular genetics
July 15, 2002
- Agency: NIGMS NIH HHS, Id: R01 GM053034
- Agency: NINDS NIH HHS, Id: R01 NS041617
- Agency: NIGMS NIH HHS, Id: R01-GM53034
- Agency: NINDS NIH HHS, Id: R01-NS41617
- Agency: NIGMS NIH HHS, Id: T32-GM08613
- Agency: NICHD NIH HHS, Id: T32-HD07518
- Carrier Proteins
- Coiled Bodies
- Cyclic AMP Response Element-Binding Protein
- HeLa Cells
- Nerve Tissue Proteins
- RNA Cap-Binding Proteins
- RNA-Binding Proteins
- Receptors, Cytoplasmic and Nuclear
- Ribonucleoproteins, Small Nuclear
- SMN Complex Proteins
- beta Karyopherins
- Spinal muscular atrophy-2 is related to genes SMN1, SMA1, SMA2, SMA3, SMA4 which are autosomal recessive according to the OMIM database.
- Spinal muscular atrophy-1 is related to genes SMN1, SMA1, SMA2, SMA3, SMA4 which are autosomal recessive according to the OMIM database.
- Spinal muscular atrophy-4 is related to genes SMN1, SMA1, SMA2, SMA3, SMA4 which are autosomal recessive according to the OMIM database.
- Spinal muscular atrophy-3 is related to genes SMN1, SMA1, SMA2, SMA3, SMA4 which are autosomal recessive according to the OMIM database.