Year: 2009
Type: article
Abstract: In Trypanosomatids, tRNAs are transcribed in the nucleus and imported from the cytosol into the mitochondrion.The only tRNA Trp encoded within the nucleus of these organisms contains a CCA anticodon that can decode the UGG codons in the cytosol, but is unable to decode the UGA tryptophan codons in the mitochondria.Trypanosomatids have evolved a tRNA editing mechanism that specifically changes the first position of the anticodon of tRNA Trp CCA from C 34 to U 34 to enable decoding of UGA codons as tryptophan.In addition to this editing event which occurs within the mitochondrion, tRNA Trp undergoes a number of post-transcriptional modifications in the anticodon stem loop before and after mitochondrial import.Notably, position 33, which is not modified in any other known tRNA, is thiolated.The focus of this research is on how the cells regulate editing and modification in the mitochondria of trypanosomes.We have hypothesized that thiolation of the normally unmodified U 33 is a means of controlling C to U editing of tRNA Trp in Trypanosomatids and thus is important for iii cell viability.In E. coli, formation of s 2 U in tRNA is mediated by the cysteine desulfurase, IscS.In Trypanosoma brucei there are two IscS homologues, acytosolic protein and a protein targeted to the mitochondria.We found that the mitochondria-targeted IscS is essential for viability and for s 2 U formation in both cytosolic and mitochondrial tRNAs.Meanwhile the cytosolic protein is not essential for thiolation of uridine at the 2 position.We also show that thiolation of U 33 is a negative determinant for editing and a means to keep editing levels down.Furthermore, our findings show a stability role for the thiolation at the wobble position.Dedicated to my family and friends, especially
Author: Jessica M. Wohlgamuth-Benedum
Institution: The Ohio State University
Language: English
Subfield: Molecular Biology
Domain: Life Sciences
Open Access status: green
OpenAlex ID: W79128159