A doughnut-shaped heteromer of human Sm-like proteins binds to the 3 '-endof U6 snRNA, thereby facilitating U4/U6 duplex formation in vitro

We describe the isolation and molecular characterization of seven distinct proteins present in human [U4/U6.U5] tri-snRNPs. These proteins exhibit cle ar homology to the Sm proteins and are thus denoted LSm (like Sm) proteins. Purified LSm proteins form a heteromer that is stable even in the absence of RNA and exhibits a doughnut shape under the electron microscope, with st riking similarity to the Sm core RNP structure. The purified LSm heteromer binds specifically to U6 snRNA, requiring the 3'-terminal U-tract for compl ex formation. The 3'-end of U6 snRNA was also co-precipitated with LSm prot eins after digestion of isolated tri-snRNPs with RNaseT(1). Importantly, th e LSm proteins did not bind to the U-rich Sm sites of intact U1, U2, U4 or U5 snRNAs, indicating that they can only interact with a 3'-terminal U-trac t. Finally, we show that the LSm proteins facilitate the formation of U4/U6 RNA duplices in vitro, suggesting that the LSm proteins may play a role in U4/U6 snRNP formation.