Coordination of tRNA nuclear export with processing of tRNA.
Eukaryotic tRNAs are synthesized in the nucleus and need to be exported to the cytoplasm where they function in translation. tRNA export is mediated by exportin-t, which binds tRNA directly and with high affinity. tRNAs are initially synthesized as precursor molecules. Maturation to functional tRNA takes place in the nucleus, precedes export, and includes trimming of the 5' and 3' ends, posttranscriptional addition of the 3' CCA end, nucleoside modifications, and in some cases splicing. Here we address the question of how tRNA maturation is coordinated with export and thus how cytoplasmic accumulation of inactive maturation intermediates is avoided. This could, in principle, be achieved by nuclear retention of immature tRNA or by selective export of the fully mature form. We show that exportin-t has a strong preference for tRNA with correctly processed 5' and 3' ends and nucleoside modification. tRNA recognition by exportin-t can thus be considered as a quality control mechanism for these maturation steps prior to tRNA export. Surprisingly however, exportin-t can efficiently bind unspliced tRNA and intron-containing tRNA is exported when the rate of splicing is slow. During characterization of the exportin-t/tRNA interaction we found that exportin-t recognizes features in the tRNA that are conserved between prokaryotic and eukaryotic tRNAs. Our data suggest that correct tRNA shape, the 5' and 3' terminal ends, and the TpsiC loop are critical for exportin-t binding.
Lipowsky
G
G
Zentrum für Molekulare Biologie der Universität Heidelberg, Germany.
Bischoff
F R
FR
Izaurralde
E
E
Kutay
U
U
Schäfer
S
S
Gross
H J
HJ
Beier
H
H
Görlich
D
D
D000818:Animals; D002352:Carrier Proteins / Q000235:genetics* / Q000378:metabolism; D002467:Cell Nucleus / Q000235:genetics; D007438:Introns / Q000235:genetics; D008845:Microinjections; D009154:Mutation; D029543:Nucleocytoplasmic Transport Proteins; D009865:Oocytes / Q000378:metabolism; D017393:RNA Editing / Q000235:genetics; D012322:RNA Precursors / Q000235:genetics; D012323:RNA Processing, Post-Transcriptional / Q000235:genetics*; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D012343:RNA, Transfer / Q000235:genetics* / Q000378:metabolism; D012357:RNA, Transfer, Lys / Q000235:genetics / Q000378:metabolism; D016601:RNA-Binding Proteins / Q000235:genetics; D014981:Xenopus
D002352:Carrier Proteins; D029543:Nucleocytoplasmic Transport Proteins; D012322:RNA Precursors; D012333:RNA, Messenger; D012357:RNA, Transfer, Lys; D016601:RNA-Binding Proteins; D012343:RNA, Transfer