SUMO modification of heterogeneous nuclear ribonucleoproteins.
Small ubiquitin-related modifiers (SUMOs) are proteins that are posttranslationally conjugated to other cellular proteins, particularly those that localize and function in the nucleus. Enzymes regulating SUMO modification localize in part to nuclear pore complexes (NPCs), indicating that modification of some proteins may occur as they are translocated between the nucleus and the cytoplasm. Substrates that are regulated by SUMO modification at NPCs, however, have not been previously identified. Among the most abundant cargos transported through NPCs are the heterogeneous nuclear ribonucleoproteins (hnRNPs). HnRNPs are involved in various aspects of mRNA biogenesis, including regulation of pre-mRNA splicing and nuclear export. Here, we demonstrate that two subsets of hnRNPs, the hnRNP C and M proteins, are substrates for SUMO modification. We demonstrate that the hnRNP C proteins are modified by SUMO at a single lysine residue, K237, and that SUMO modification at this site decreases their binding to nucleic acids. We also show that Nup358, a SUMO E3 ligase associated with the cytoplasmic fibrils of NPCs, enhances the SUMO modification of the hnRNP C and M proteins. Based on our findings, we propose that SUMO modification of the hnRNP C and M proteins may occur at NPCs and facilitate the nucleocytoplasmic transport of mRNAs.
Vassileva
Maria T
MT
Department of Biochemistry and Molecular Biology, Bloomberg School of Public Health, Johns Hopkins University, Baltimore, Maryland 21205, USA.
Matunis
Michael J
MJ
D021581:Active Transport, Cell Nucleus / Q000502:physiology; D000818:Animals; D002467:Cell Nucleus / Q000378:metabolism*; D004277:DNA, Single-Stranded / Q000378:metabolism; D006367:HeLa Cells; D022781:Hepatocytes / Q000166:cytology; D034441:Heterogeneous-Nuclear Ribonucleoproteins / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D008239:Lysine / Q000378:metabolism; D046911:Macromolecular Substances; D018832:Molecular Chaperones / Q000378:metabolism; D009685:Nuclear Envelope / Q000378:metabolism; D028861:Nuclear Pore Complex Proteins / Q000378:metabolism; D020033:Protein Isoforms / Q000235:genetics / Q000378:metabolism; D011499:Protein Processing, Post-Translational; D020836:Protein Structure, Quaternary; D051381:Rats; D025842:SUMO-1 Protein / Q000235:genetics / Q000378:metabolism*
D004277:DNA, Single-Stranded; D034441:Heterogeneous-Nuclear Ribonucleoproteins; D046911:Macromolecular Substances; D018832:Molecular Chaperones; D028861:Nuclear Pore Complex Proteins; D020033:Protein Isoforms; D025842:SUMO-1 Protein; C094493:ran-binding protein 2; D008239:Lysine