Multiple functional interactions between components of the Lsm2-Lsm8 complex, U6 snRNA, and the yeast La protein

The U6 small nuclear ribonucleoprotein is a critical component of the eukar yotic spliceosome. The first protein that binds the U6 snRNA is tile La pro tein, an abundant phosphoprotein that binds the 3 ' end of many nascent sma ll RNAs. A complex of seven Sm-like proteins, Lsm2-Lsm8, also binds the 3 ' end of U6 snRNA. A mutation within the Sm motif of Lsm8p causes Saccharomy ces cerevisiae cells to require the La protein Lhp1p to stabilize nascent U 6 snRNA. Here we describe functional interactions between Lhp1p, the Lsm pr oteins, and U6 snRNA. LSM2 and LSM4, but not other LSM genes, act as allele -specific, low-copy suppressors of mutations in Lsm8p. Overexpression of LS M2 in the lsm8 mutant strain increases the levels of both Lsm8p and U6 snRN Ps. In the presence of extra U6 snRNA genes, LSM8 becomes dispensable for g rowth, suggesting that the only essential function of LSM8 is in U6 RNA bio genesis or function. Furthermore, deletions of LSM5, LSM6 or LSM7 cause LHP 1 to become required for growth. Our experiments are consistent with a mode l in which Lsm2p and Lsm4p contact Lsm8p in the Lsm2-Lsm8 ring and suggest that Lhp1p acts redundantly with the entire Lsm2-Lsm8 complex to stabilize nascent U6 snRNA.