Molecular and functional characterization of a Trypanosoma cruzi nuclear adenylate kinase isoform

CAMARA, MARIA DE LOS MILAGROS; BOUVIER, LEON; CANEPA, GASPAR; MIRANDA, MARIANA; PEREIRA, CA

PLOS NEGLECTED TROPICAL DISEASES

PUBLIC LIBRARY SCIENCE

Lugar: San Francisco; Año: 2013 vol. 7 p. 2044 - 2047

1935-2735

Trypanosoma cruzi, the etiological agent of Chagas? disease, is an early divergent eukaryotein which control of gene expression relies mainly in post-transcriptional mechanisms.Transcription levels are globally up and down regulated during the transition betweenproliferating and non-proliferating life-cycle stages. In this work we characterized a nuclearadenylate kinase isoform (TcADKn) that is involved in ribosome biogenesis. Nuclearadenylate kinases have been recently described in a few organisms, being all related toRNA metabolism.Depending on active transcription and translation, TcADKn localizes in the nucleolus or thecytoplasm. A non-canonical nuclear localization signal was mapped towards the N-terminalof the protein, being the phosphate-binding loop essential for its localization. In addition,TcADKn nuclear exportation depends on the nuclear exportation adapter CRM1. TcADKnnuclear shuttling is governed by nutrient availability, oxidative stress and by the equivalent inT. cruzi of the mammalian TOR (Target of Rapamycin) pathway. One of the possiblebiological functions of TcADKn is ribosomal 18S RNA processing by direct interaction withribosomal protein TcRps14. Finally, TcADKn expression is regulated by its 3? UTR mRNA.Depending on extracellular conditions, cells modulate protein translation rates regulatingribosome biogenesis and nuclear adenylate kinases are probably key components in theseprocesses.