Talk on Saturday 08:45-09:00am submitted by Kunal Chatterjee
Sharing the load: Mex67-Mtr2 co-functions with Los1 in primary tRNA nuclear export
Kunal Chatterjee (The Ohio State University Comprehensive Cancer Research Centre, Centre for RNA Biology, Department of Molecular Genetics, The Ohio State University.), Shubhra Majumder, Yao Wan, Vijay Shah, Jungian Wu, Hsiao-Yun Huang, (Department of Molecular Genetics, Centre for RNA Biology, The Ohio State University), Anita K. Hopper (Department of Molecular Genetics, Centre for RNA Biology, The Ohio State University)
tRNAs perform essential role of delivering amino acids to the cytoplasmic protein synthesis machinery. To execute this role in protein production, eukaryotic tRNAs must be escorted out of the nucleus, their site of synthesis, to the cytoplasm, their site of function. Via primary nuclear export, newly transcribed, end matured, partially modified tRNAs are shuttled to the cytoplasm, where, in yeast, the tRNA splicing machinery is located. Genetic and biochemical studies have identified a set of RanGTPase binding proteins, β-importins, implicated in this tRNA movement. Two members of the β-importin family, Los1 (Exportin-t in vertebrates) and Msn5 (Exportin 5) serve overlapping but distinct functions in tRNA export. Although Los1 and Msn5 both participate in tRNA nuclear export, they cannot be the only nuclear exporters for tRNAs in yeast as los1Δ msn5Δ double mutant cells are viable. An unbiased comprehensive screening representing ~90% of the total yeast proteome recently conducted in our laboratory uncovered novel proteins involved in tRNA subcellular dynamics. Two such proteins Mex67 (vertebrate TAP) and Mtr2 (vertebrate p15), which are known to be mRNA nuclear exporters, when inactivated, accumulate end-matured, unspliced tRNAs in yeast nuclei. Remarkably, merely 5-fold over-expression of Mex67-Mtr2 substitutes for Los1 in los1Δ cells. Moreover, in vivo co-immunoprecipitation assays with Mex67 document that the Mex67 binds tRNAs. We also show that tRNA exporters surprisingly exhibit differential tRNA substrate preferences, possibly indicating that the proteome can be regulated at the step of tRNA nuclear export. Thus, our data show that the mRNA export machinery, Mex67-Mtr2, co-functions with Los1, in primary nuclear export for a subset of yeast tRNAs.
Keywords: tRNA subcellular dynamics, tRNA trafficking, Sachharomyces cerevisiae