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Science 29 November 2002:
Vol. 298. no. 5599, pp. 1775 - 1779
DOI: 10.1126/science.1074962
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Reports

Essential Role for the SMN Complex in the Specificity of snRNP Assembly

Livio Pellizzoni,* Jeongsik Yong, Gideon Dreyfussdagger

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.

Howard Hughes Medical Institute and Department of Biochemistry and Biophysics, University of Pennsylvania School of Medicine, Philadelphia, PA 19104-6148, USA.
*   Present address: Institute of Cell Biology, Consiglio Nazionale delle Ricerche, "Campus Adriano-Buzzati-Traverso," IBC 00016, Monterotondo Scalo, Rome, Italy.

dagger    To whom correspondence should be addressed. E-mail: gdreyfuss{at}hhmi.upenn.edu

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