pICln inhibits snRNP biogenesis by binding core spliceosomal proteins

The U1, U2, U4, U5, and U6 small nuclear ribonucleoproteins (snRNPs) form e ssential components of spliceosomes, the machinery that removes introns fro m pre-mRNAs in eukaryotic cells. A critical initial step in the complex pro cess of snRNP biogenesis is the assembly of a group of common core proteins (Sm proteins) on spliceosomal snRNA. In this study we show by multiple ind ependent methods that the protein pICln associates with Sm proteins in vivo and in vitro. The binding of pICln to Sm proteins interferes with Sm prote in assembly on spliceosomal snRNAs and inhibits import of snRNAs into the n ucleus. Furthermore, pICln prevents the interaction of Sm proteins with the survival of motor neurons (SMN) protein, an interaction that has been show n to be critical for snRNP biogenesis. These findings lead us to propose a model in which pICln participates in the regulation of snRNP biogenesis, at least in part by interfering with Sm protein interaction with SMN protein.