snRNAs contain specific SMN-binding domains that are essential for snRNP assembly.
To serve in its function as an assembly machine for spliceosomal small nuclear ribonucleoprotein particles (snRNPs), the survival of motor neurons (SMN) protein complex binds directly to the Sm proteins and the U snRNAs. A specific domain unique to U1 snRNA, stem-loop 1 (SL1), is required for SMN complex binding and U1 snRNP Sm core assembly. Here, we show that each of the major spliceosomal U snRNAs (U2, U4, and U5), as well as the minor splicing pathway U11 snRNA, contains a domain to which the SMN complex binds directly and with remarkable affinity (low nanomolar concentration). The SMN-binding domains of the U snRNAs do not have any significant nucleotide sequence similarity yet they compete for binding to the SMN complex in a manner that suggests the presence of at least two binding sites. Furthermore, the SMN complex-binding domain and the Sm site are both necessary and sufficient for Sm core assembly and their relative positions are critical for snRNP assembly. These findings indicate that the SMN complex stringently scrutinizes RNAs for specific structural features that are not obvious from the sequence of the RNAs but are required for their identification as bona fide snRNAs. It is likely that this surveillance capacity of the SMN complex ensures assembly of Sm cores on the correct RNAs only and prevents illicit, potentially deleterious, assembly of Sm cores on random RNAs.
Yong
Jeongsik
J
Department of Biochemistry and Biophysics, Howard Hughes Medical Institute, University of Pennsylvania School of Medicine, Philadelphia, Pennsylvania 19104-6148, USA.
Golembe
Tracey J
TJ
Battle
Daniel J
DJ
Pellizzoni
Livio
L
Dreyfuss
Gideon
G
D000818:Animals; D001324:Autoantigens; D006367:HeLa Cells; D006801:Humans; D046911:Macromolecular Substances; D009046:Motor Neurons / Q000378:metabolism; D009690:Nucleic Acid Conformation; D009865:Oocytes / Q000502:physiology; D011485:Protein Binding; D017434:Protein Structure, Tertiary; D012342:RNA, Small Nuclear / Q000378:metabolism*; D017411:Ribonucleoproteins, Small Nuclear / Q000235:genetics / Q000378:metabolism*; D017381:Spliceosomes / Q000378:metabolism; D014982:Xenopus laevis; D055517:snRNP Core Proteins
D001324:Autoantigens; D046911:Macromolecular Substances; D012342:RNA, Small Nuclear; D017411:Ribonucleoproteins, Small Nuclear; C526417:SNRPN protein, human; D055517:snRNP Core Proteins