High levels of tRNA abundance and alteration of tRNA charging by bortezomib in multiple myeloma.
In multiple myeloma (MM), malignant plasma cells produce large amounts of antibodies and have highly active protein translational machinery. It is not known whether regulation of the abundance and aminoacylation (charging) of transfer RNA (tRNA) takes place in myeloma cells to accommodate for the increased amount of protein translation. Using tRNA-specific microarrays, we demonstrate that tRNA levels are significantly elevated in MM cell lines compared to normal bone marrow cells. We furthermore show that the addition of the proteasome inhibitor, bortezomib (Velcade, PS-341) results in decreased charging levels of tRNAs, in particular those coding for hydrophobic amino acids. These results suggest that tRNA properties are altered in MM to accommodate for its increased need for protein translation, and that proteasome inhibition directly impacts protein synthesis in MM through effects on tRNA charging.
Zhou
Ying
Y
Department of Medicine, University of Chicago, Chicago, IL 60637, USA.
Goodenbour
Jeffrey M
JM
Godley
Lucy A
LA
Wickrema
Amittha
A
Pan
Tao
T
D001897:Boronic Acids / Q000494:pharmacology*; D000069286:Bortezomib; D045744:Cell Line, Tumor; D006801:Humans; D009101:Multiple Myeloma / Q000378:metabolism*; D020411:Oligonucleotide Array Sequence Analysis; D011480:Protease Inhibitors / Q000494:pharmacology*; D061988:Proteasome Inhibitors; D014176:Protein Biosynthesis / Q000187:drug effects; D021381:Protein Transport / Q000187:drug effects; D011719:Pyrazines / Q000494:pharmacology*; D012343:RNA, Transfer / Q000378:metabolism*; D046249:Transfer RNA Aminoacylation / Q000187:drug effects*
D001897:Boronic Acids; D011480:Protease Inhibitors; D061988:Proteasome Inhibitors; D011719:Pyrazines; D000069286:Bortezomib; D012343:RNA, Transfer