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We are currently focusing on the assignment of other activities to genes, and on two aspects of the biology of modifications: First, we are investigating the roles of modifications. We recently found evidence that lack of certain modifications can lead to rapid degradation of specific mature tRNAs, suggesting the existence of a quality control pathway that monitors the integrity of tRNA. We are currently working to define the components of this rapid tRNA decay pathway, the mechanism by which tRNAs are targeted for turnover, and the conditions under which this pathway is used. Second, we are defining the mechanisms by which modification enzymes recognize and act on their specific tRNA substrates. Since modifications have crucial roles in the cell, incorrect modification of a tRNA is likely to have catastrophic effects. We recently found that recognition of the tRNAHis anticodon is necessary and sufficient for Thg1 to add a guanine nucleotide to the 5' end of the tRNA, a reaction that is essential in wild type cells for proper translation. We are currently examining other modification enzymes to uncover the different mechanisms by which specificity is attained.
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Thareendra De Zoysa,Alayna C. Hauke, Nivedita R. Iyer,Erin Marcus, Sarah M. Ostrowski, Franziska Stegemann,Dmitri N. Ermolenko,Justin C. Fay,Eric M. Phizicky
RNA (New York, N.Y.)no. 7 (2023): 898-957
Holly M Funk,Daisy J DiVita,Hannah E Sizemore,Kendal Wehrle, Catherine L W Miller, Morgan E Fraley, Alex K Mullins,Adrian R Guy,Eric M Phizicky,Michael P Guy
bioRxiv (Cold Spring Harbor Laboratory) (2021)
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