Retrograde nuclear import of tRNA precursors is required for modified base biogenesis in yeast

• Published in: Proceedings of the National Academy of Sciences - PNAS 2011-06, Vol.108 (26), p.10502-10507
• Main Authors: Ohira, Takayuki, Suzuki, Tsutomu
• Format: Article
• Language: English
• Subjects: Anticodon; Anticodons; Base Sequence; binding proteins; Binding sites; biogenesis; Biological Sciences; Biological Transport; Biosynthesis; Cell Nucleus - metabolism; Chromatography, Affinity; Cytoplasm; DNA Primers; Enzymes; eukaryotic cells; Glucose; Introns; Mass Spectrometry; Molecular Sequence Data; Molecules; Nuclear transport; Nucleic Acid Conformation; Nucleosides; physiological transport; RNA; RNA precursors; RNA Precursors - chemistry; RNA Precursors - metabolism; RNA Splicing; RNA, Fungal - chemistry; RNA, Fungal - metabolism; RNA, Transfer, Phe - chemistry; RNA, Transfer, Phe - metabolism; Saccharomyces cerevisiae; Saccharomyces cerevisiae - genetics; Saccharomyces cerevisiae - metabolism; Splicing; Starvation; Transfer RNA; tRNA; Yeast; Yeasts
• ISSN: 0027-8424; 1091-6490
• DOI: 10.1073/pnas.1105645108

The retrograde movement of tRNAs from the cytoplasm to the nucleus occurs constitutively in eukaryotic cells but its functional significance remains unclear. We show evidence suggesting that in Saccharomyces cerevisiae, a spliced tRNA precursor must be imported into the nucleus before the biogenesis of a modified base can occur. Wybutosine (yW) is a modified base adjacent to the anticodon of tRNAPhe and is required for accurate decoding. Glucose starvation or overexpression of the nuclear tRNA binding protein Trz1p both caused nuclear retention of cytoplasmic tRNAs, impaired the yW synthesis, and induced the accumulation of its intermediate, N¹-methylgunanosine (m¹G), showing that the postspliced tRNAPhe is imported to the nucleus, where m¹G is formed by Trm5p, after which it is reexported to the cytoplasm, where the yW synthesis is completed by cytoplasmic enzymes.