A role for the yeast La protein in U6 snRNP assembly: evidence that the Laprotein is a molecular chaperone for RNA polymerase III transcripts

The first protein that binds to all newly synthesized RNA polymerase III tr anscripts is a highly conserved phosphoprotein known as the La autoantigen, Although binding by the yeast La protein Lhp1p to pre-tRNAs is required fo r the normal pathway of tRNA maturation, the role of the La protein in the biogenesis of other polymerase III transcripts has been unclear. We identif ied a mutation in a novel component of the U6 snRNP that causes yeast cells to require Lhp1p for growth. This protein, Lsm8p, is a member of a family of proteins, known as Sm-like proteins, that shares two conserved motifs wi th the core Sm proteins of the U1, U2, U4 and U5 snRNPs, The lsm8-1 cells h ave drastically reduced levels of the mature U6 snRNP, consistent with a de fect in U6 snRNP assembly. In these cells, Lhp1p stabilizes newly synthesiz ed U6 RNA, thus facilitating assembly of the RNA into the U6 snRNP, These r esults provide evidence that Lhp1p is a molecular chaperone for polymerase III-transcribed RNAs and implicate Lsm8p as a key component in the very ear ly steps of U6 snRNP assembly.