Trm10 Active Site

OVERVIEW                         THG1                         TRM10 


The tRNA m1G9 methyltransferase (Trm10)

RNA-protein interactions play critical roles in biology. Often, proteins that interact with RNAs are required to discriminate between highly similar RNA substrates to select their targets for enzyme activity. Many decades of research into tRNA recognition by aminoacyl-tRNA synthetases has provided some guiding principles for how tRNA species that share common sequence features are recognized selectively by their cognate synthetase enzymes. However, several tRNA modification enzymes, including Trm10, recognize multiple tRNA species that do not share identifiable sequence similarity, and thus the basis for tRNA recognition by these enzymes is unknown. We are working to identify the molecular basis for tRNA substrate recognition by Trm10, because it is an ideal system to understand protein-RNA interactions that are not guided by selection of specific nucleotide sequence identities

A second goal of our work with Trm10 is to understand the potential involvement of Trm10 family members in processes other than tRNA modification. In 2008, a human homolog of Trm10 was implicated in 5′-tRNA processing in mitochondria by virtue of its participation in an unusual protein-only form of the enzyme Ribonuclease P. We are investigating this, and other examples, of Trm10 function in higher eukaryotes.


Selected Publications:

  1. Krishnamohan A., Jackman J.E.,  Mechanistic features of the atypical tRNA m1G9 SPOUT methyltransferase, Trm10. Nucleic Acids Res. 2017 Sep 6;45(15):9019-9029. doi: 10.1093/nar/gkx620. Pubmed
  2. Swinehart W.E., Henderson J.C., Jackman J.E. Unexpected expansion of tRNA substrate recognition by the yeast m1G9 methyltransferase Trm10. RNA. 2013 Aug;19(8):1137-46. doi: 10.1261/rna.039651.113. PubMed
  3. Jackman J.E., Montange R.K., Malik H.S., Phizicky E.M. Identification of the yeast gene encoding the tRNA m1G methyltransferase responsible for modification at position 9 RNA. 2003 May;9(5):574-85. PubMed