Using yeast, S. cerevisiae, as a model system we employ a multidiscipline approach to study the mechanisms of distribution of RNAs and proteins between the nucleus and cytoplasm.
A major focus is intracellular trafficking of tRNAs. Nearly all RNAs that function in protein synthesis are generated in the nucleus, but function in the cytoplasm. Conversely, many proteins generated in the cytoplasm, function in the nucleus. Employing genetic, genome-wide, biochemical, and cell biological approaches we learned that there are parallel nuclear export pathways, that export is quality controlled by components of the translation machinery that previously were thought to reside exclusively in the cytoplasm, and that nucleus/cytoplasm exchange and cellular metabolism are intricately connected. Importantly, we showed that tRNAs move retrograde from the cytoplasm to the nucleus and accumulate there under particular stress conditions - a surprising discovery. Retrograde tRNA movement also occurs in metazoans. The tRNA retrograde movement serves to regulate protein synthesis under conditions of nutrient stress by separating tRNA from the cytoplasmic translation machinery as well as a tRNA quality control mechanism.
Selected Recent (2013- 2018) Publications
(see CV for full publication list)
Selected Recent Publications form the Hopper lab (2013-2018)
- Wan, Y., A.K. Hopper. From powerhouse to processing plant: conserved roles of mitochondrial outer membrane proteins in tRNA splicing. Genes Dev., in revision, June 2018.
- Wan, Y., A. K. Hopper. Size matters: conserved proteins function in length-dependent nuclear export of circular RNAs. Genes and Development 32: 600-601 (2018) (Outlook commentary).
- Chatterjee, K., R.T. Nostramo, Y. Wan, A.K. Hopper. tRNA dynamics between the nucleus, cytoplasm and mitochondrial surface: location, location, location. BBA – Gene Regulatory Mechanisms 1861:373-386 (2018). Peer evaluated invited review.
- Chatterjee, K., S. Majumder, Y. Wan, V. Shah, J. Wu, H-Y Huang, A.K. Hopper. Sharing the load: Mex67-Mtr2 co-functions with Los1 in primary tRNA nuclear export, Genes Dev. 31:2186-2198 (2017).
- Huang H.-Y., A.K. Hopper. Multiple layers of stress-induced regulation in tRNA Biology. Life: 6: pii: E16. (2016). Peer-evaluated review.
- Foretek, D., J. Wu, A.K. Hopper, M. Boguta. Control of Saccharomyces cerevisiae pre-tRNA processing by environmental conditions. RNA 22:390349 (2016).
- Wu, J., A. Bao, K. Chatterjee, A.K. Hopper. Genome-wide screen uncovers novel pathways for tRNA processing and nuclear-cytoplasmic dynamics. Genes Dev. 29:2633-2644 (2015).
- Phizicky, E.M., A.K. Hopper. tRNA processing, modification, and subcellular dynamics: past, present, and future RNA 21:483-485 (2015).
- Huang, H.-Y., A.K. Hopper. In vivo biochemical analyses reveal distinct roles of β-importins and eEF1A in tRNA subcellular traffic. Genes Dev. 29:772-783 (2015).
- Hopper, A.K., H.Y. Huang. Quality control pathways for nuclear-encoded eukaryotic tRNA biosynthesis and subcellular trafficking. Mol. Cell. Biol. 35:2052-2058 (2015). Peer-evaluated review.
- Huang, H.-Y., A.K. Hopper. Separate responses of karyopherins to glucose and amino acid availability regulate nucleocytoplasmic transport. Mol. Biol. Cell. 25:2840-2852 (2014).
- Wu, J., A.K. Hopper. Healing for destruction: tRNA intron degradation in yeast is a two-step cytoplasmic process catalyzed by tRNA ligase Rlg1 and 5’-to-3’ exonuclease Xrn1. Genes Dev. 28:1556-1561 (2014).
- Diaz, G, T.A. Harchar, T.-P. Lai, Shen, K.-F. and A.K. Hopper. Requirement of the spindle pole body for targeting/tethering proteins to the inner nuclear membrane. Nucleus 5:1-15 (2014).
- Kramer, E.B. and A.K. Hopper. Retrograde tRNA nuclear import provides a new level of tRNA quality control in Saccharomyces cerevisiae. Proc. Natl. Acad. Sci. 110:21042-21047 (2013).
- Chu, H.-Y. and A.K. Hopper. Genome-wide investigation of the role of the nucleus-cyotplasm trafficking pathway in regulation of the yeast S. cerevisiae transcriptome and proteome. Mol. Cell. Biol. 33:4242-4254 (2013).
- Pratt-Hyatt, M. D.A. Pai, A. Haeusler, G. G. Wozniak, P.D. Good, E.L. Miller, I.X. McLeod, J.R. Yates III, A.K. Hopper, D.R. Engelke. Mod5 protein binds to tRNA gene complexes and affects local transcriptional silencing. Proc. Natl. Acad. Sci. 110:E3081-9 (2013).
- Wu, J., H.-Y. Huang, A.K. Hopper. A rapid and sensitive nonradioactive method applicable for genome-wide analysis of Saccharomyces cerevisiae genes involved in small RNA biology. Yeast 30:119-128 (2013).
- Hopper, A.K. tRNA post-transcriptional processing, turnover, and subcellular dynamics in the yeast Saccharomyces cerevisiae. Genetics 194:43-67 (2013).
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