Poster abstracts
Poster number 29 submitted by Shubhra Majumder
Mex67-Mtr2, an mRNA exporter, also serves as a nuclear exporter of pre-tRNAs
Shubhra Majumder (Research Associate, Dept of Molecular Genetics, Center for RNA Biology), Kunal Chatterjee (Post-doctoral fellow, Dept of Molecular Genetics, Center for RNA Biology), Anita K. Hopper (Professor, Dept of Molecular Genetics, Center for RNA Biology)
Abstract:
Transfer RNAs (tRNAs) that are essential for translation, are transcribed in nucleus and exported to cytoplasm. Recent studies discovered that mature tRNAs return to nucleus in a retrograde fashion, and this retrograde nuclear import functions in tRNA quality control, particularly to proofread tRNA end-processing and hypomodifications of nucleotides. tRNA genes often contain introns, and intron splicing is essential for the function of those tRNAs. In budding yeast, end-processed, and modified intron-containing pre-tRNAs are exported to cytoplasm, primarily by the function of Los1, the dedicated exporter for tRNAs. The cytoplasmic tRNAs are constitutively imported into the nucleus after being spliced on the mitochondrial surface. Mature tRNAs attached with appropriate amino acid moiety are then re-exported to cytoplasm to participate in translation. My studies revealed that the Los1-mediated export pathway proofreads processing of 5’/3’ ends of pre-tRNAs, as 5’-end extended, spliced tRNAs (such as tRNAIluUAU) accumulate in los1∆ cells. However, m22G26 hypomodified aberrant tRNAs (such as tRNALysUUU) do not accumulate in those cells, suggesting that the Los1-mediated export pathway may not proofread nucleotide modifications. Also, LOS1 is not essential in yeast cells. A recent genome-wide screen from our lab identified the Mex67-Mtr2 heterodimer, a well-known exporter for mRNAs to serve as a potential nuclear exporter for tRNAs. My data documents that, while overexpression of Mex67-Mtr2 heterodimer suppresses the nuclear accumulation of intron-containing tRNAs in los1∆ cells, it failed to efficiently proofread the ends of those tRNAs during nuclear export, and could not suppress the accumulation of 5’-end containing spliced tRNAs. Overall, my data supports the notion that the function of Mex67-Mtr2 complex in pre-tRNA nuclear export is an error-prone process. Nevertheless, this process may serve as an auxiliary tRNA nuclear export mechanism in conditions when Los1 function is attenuated (such as in amino acid starvation in yeast). Such conditions likely rely on the subsequent retrograde nuclear import pathway for tRNA quality control that is critical for translation and cell viability.
Keywords: tRNA nuclear export, tRNA quality control, translation