The SMN complex: an assembly machine for RNPs.
In eukaryotic cells, the biogenesis of spliceosomal small nuclear ribonucleoproteins (snRNPs) and likely other RNPs is mediated by an assemblyosome, the survival of motor neurons (SMN) complex. The SMN complex, composed of SMN and the Gemins (2-7), binds to the Sm proteins and to snRNAs and constructs the heptameric rings, the common cores of Sm proteins, on the Sm site (AU(56)G) of the snRNAs. We have determined the specific sequence and structural features of snRNAs for binding to the SMN complex and Sm core assembly. The minimal SMN complex-binding domain in snRNAs (except U1) is composed of an Sm site and a closely adjacent 3'stem-loop. Remarkably, the specific sequence of the stemloop is not important for SMN complex binding, but it must be located within a short distance of the 3'end of the RNA for an Sm core to assemble. This minimal snRNA-defining "snRNP code" is recognized by the SMN complex, which binds to it directly and with high affinity and assembles the Sm core. The recognition of the snRNAs is provided by Gemin5, a component of the SMN complex that directly binds the snRNP code. Gemin5 is a novel RNA-binding protein that is critical for snRNP biogenesis. Thus, the SMN complex is the identifier, as well as assembler, of the abundant class of snRNAs in cells. The function of the SMN complex, previously unanticipated because RNP biogenesis was believed to occur by self-assembly, confers stringent specificity on otherwise potentially illicit RNA-protein interactions.
Battle
D J
DJ
Howard Hughes Medical Institute and Department of Biochemistry and Biophysics, University of Pennsylvania School of Medicine, Philadelphia, Pennsylvania 19104-6148, USA.
Kasim
M
M
Yong
J
J
Lotti
F
F
Lau
C-K
CK
Mouaikel
J
J
Zhang
Z
Z
Han
K
K
Wan
L
L
Dreyfuss
G
G
D001483:Base Sequence; D017362:Cyclic AMP Response Element-Binding Protein / Q000737:chemistry* / Q000378:metabolism*; D006367:HeLa Cells; D006801:Humans; D008954:Models, Biological; D008969:Molecular Sequence Data; D046912:Multiprotein Complexes; D009419:Nerve Tissue Proteins / Q000737:chemistry* / Q000378:metabolism*; D009690:Nucleic Acid Conformation; D012342:RNA, Small Nuclear / Q000096:biosynthesis / Q000737:chemistry / Q000235:genetics; D016601:RNA-Binding Proteins / Q000737:chemistry* / Q000378:metabolism*; D012261:Ribonucleoproteins / Q000737:chemistry* / Q000378:metabolism*; D017411:Ribonucleoproteins, Small Nuclear / Q000096:biosynthesis / Q000737:chemistry / Q000378:metabolism; D055532:SMN Complex Proteins; D017381:Spliceosomes / Q000378:metabolism
D017362:Cyclic AMP Response Element-Binding Protein; C449808:GEMIN5 protein, human; D046912:Multiprotein Complexes; D009419:Nerve Tissue Proteins; D012342:RNA, Small Nuclear; D016601:RNA-Binding Proteins; D012261:Ribonucleoproteins; D017411:Ribonucleoproteins, Small Nuclear; D055532:SMN Complex Proteins