Control of transfer RNA maturation by phosphorylation of the human La antigen on Serine 366

Conversion of a nascent precursor tRNA to a mature functional species is a multipartite process that involves the sequential actions of several proces sing and modifying enzymes. La is the first protein to interact with pre-tR NAs in eukaryotes. An opal suppressor tRNA served as a functional probe to examine the activities of yeast and human (h)La proteins in this process in fission yeast. An RNA recognition motif and Walker motif in the metazoan-s pecific C-terminal domain (CTD) of hLa maintain pre-tRNA in an unprocessed state by blocking the 5'-processing site, impeding an early step in the pat hway. Faithful phosphorylation of hLa on serine 366 reverses this block and promotes tRNA maturation. The results suggest that regulation of tRNA matu ration at the level of RNase P cleavage may occur via phosphorylation of se rine 366 of hLa.