title: Essential role for the SMN complex in the specificity of snRNP assembly.
abstract: The Survival of Motor Neurons (SMN) protein, the product of the spinal muscular atrophy-determining gene, is part of a large macromolecular complex (SMN complex) that functions in the assembly of spliceosomal small nuclear ribonucleoproteins (snRNPs). Using cell extracts and purified components, we demonstrated that the SMN complex is necessary and sufficient to mediate the ATP-dependent assembly of the core of seven Sm proteins on uridine-rich, small nuclear ribonucleic acids (U snRNAs). In vitro experiments revealed strict requirements for ordered binding of the Sm proteins and the U snRNAs to the SMN complex. Importantly, the SMN complex is necessary to ensure that Sm cores assemble only on correct RNA targets and prevent their otherwise promiscuous association with other RNAs. Thus, the SMN complex functions as a specificity factor essential for the efficient assembly of Sm proteins on U snRNAs and likely protects cells from illicit, and potentially deleterious, nonspecific binding of Sm proteins to RNAs.
authors.affiliation: Howard Hughes Medical Institute and Department of Biochemistry and Biophysics, University of Pennsylvania School of Medicine, Philadelphia, PA 19104-6148, USA.
authors.forename: Livio
authors.initials: L
authors.lastname: Pellizzoni
authors.forename: Jeongsik
authors.initials: J
authors.lastname: Yong
authors.forename: Gideon
authors.initials: G
authors.lastname: Dreyfuss
mesh_terms: D000255:Adenosine Triphosphate / Q000378:metabolism; D002352:Carrier Proteins / Q000378:metabolism; D002457:Cell Extracts; D017362:Cyclic AMP Response Element-Binding Protein; D055541:DEAD Box Protein 20; D053487:DEAD-box RNA Helicases; D006367:HeLa Cells; D006801:Humans; D007700:Kinetics; D015778:Minor Histocompatibility Antigens; D008954:Models, Biological; D009419:Nerve Tissue Proteins / Q000302:isolation & purification / Q000378:metabolism*; D009687:Nuclear Proteins / Q000378:metabolism; D009843:Oligoribonucleotides / Q000378:metabolism; D011485:Protein Binding; D020365:RNA Helicases / Q000378:metabolism; D012342:RNA, Small Nuclear / Q000378:metabolism*; D016601:RNA-Binding Proteins; D017411:Ribonucleoproteins, Small Nuclear / Q000302:isolation & purification / Q000378:metabolism*; D055532:SMN Complex Proteins
chemical_list: D000255:Adenosine Triphosphate; D002352:Carrier Proteins; D002457:Cell Extracts; D017362:Cyclic AMP Response Element-Binding Protein; D055541:DEAD Box Protein 20; D053487:DEAD-box RNA Helicases; D015778:Minor Histocompatibility Antigens; D009419:Nerve Tissue Proteins; D009687:Nuclear Proteins; D009843:Oligoribonucleotides; D020365:RNA Helicases; D012342:RNA, Small Nuclear; D016601:RNA-Binding Proteins; D017411:Ribonucleoproteins, Small Nuclear; D055532:SMN Complex Proteins; C108381:GEMIN2 protein, human; C406815:GEMIN4 protein, human; C449808:GEMIN5 protein, human; C450836:GEMIN6 protein, human; C405483:U1 small nuclear RNA; C466231:GEMIN7 protein, human; C120168:DDX20 protein, human