The yeast La protein is required for the 3' endonucleolytic cleavage that matures tRNA precursors.

Although the La autoantigen binds to the 3' ends of all nascent polymerase III transcripts, its function in vivo has long been unclear. Although S. cerevisiae cells lacking the La protein homolog Lhp1p are viable, cells containing a mutation that disrupts the anticodon stem of tRNA(Ser)CGA require Lhp1p for growth. We demonstrate that for the wild-type pre-tRNA(Ser)CGA and other pre-tRNAs, Lhp1p is required for the normal endonucleolytic removal of the 3' trailer sequence. In cells lacking Lhp1p, the 3' trailer is removed by exonuclease(s). Although maturation of the mutant pre-tRNA(Ser)CGA requires Lhp1p, introduction of a second mutation that restores base pairing eliminates the requirement. We propose that binding by Lhp1p stabilizes pre-tRNAs in conformations that allow the 3' endonucleolytic cleavage to occur.