Frick Laboratory, A87
Our current understanding of nucleic acid biology indicates that RNA plays a number of diverse roles in cellular processes ranging from protein translation and gene regulation to metabolite sensing and adaptive immunity. Concomitant with this functional diversity, is the rich chemical diversity of cellular RNA. To date, over 100 structurally distinct chemical modifications have been found, including both enzymatic and non-enzymatic modifications of the canonical ribonucleotides; however, there is a major gap in our understanding of how these chemical modifications impact RNA function.
Our goal is to decipher the chemical complexity of cellular RNA. Towards this end, we are developing and employing novel approaches integrating chemistry and biology to investigate the functional significance of RNA modifications and the interplay of RNA chemistry with cellular mechanisms regulating RNA function and integrity. Our studies will rely heavily upon synthetic and chemoenzymatic strategies for generating modified nucleic acids, chemical proteomics, and quantitative cellular imaging, and aim to reveal fundamental biological mechanisms maintaining cellular homeostasis.
NSF CAREER Award (2019)
Sloan Research Fellowship (2019)
Sidney Kimmel Foundation Scholar Award (2017)
Damon Runyon Dale F. Frey Award for Breakthrough Scientists (2016)
Revson Foundation Fellowship in Biomedical Science (2014)
Damon Runyon Cancer Research Foundation Postdoctoral Fellowship (2012)
Chemical Method to Sequence 5-Formylcytosine on RNA. Li, A.; Sun, X.; Arguello, A.E.; Kleiner, R.E. ACS Chem. Biol. (2022), 17:503-508.
Reactivity-dependent profiling of RNA 5-methylcytidine dioxygenases. Arguello, A.E.; Li, A.; Sun, X.; Eggert, T.W.; Mairhofer, E.; Kleiner, R.E. Nat. Commun. (2022), 13:4176.
Live-cell RNA imaging with metabolically incorporated fluorescent nucleosides. Wang, D.; Shalamberidze, A.; Arguello, A.E.; Purse, B. Kleiner, R.E. J. Am. Chem. Soc. (2022), 144:14647-14656
Activity-based RNA-modifying enzyme probing reveals DUS3L-mediated dihydrouridylation.
Dai, W.; Li, A.; Yu, N.J.; Nguyen, T.; Leach, R.W.; Wuhr, M.; Kleiner, R.E. Nat. Chem. Biol. (2021) https://doi.org/10.1038/s41589-021-00874-8
“Cell- and Polymerase-Selective Metabolic Labeling of Cellular RNA with 2’-Azidocytidine” Wang, D.; Zhang, Y.; Kleiner, R. E. J. Am. Chem. Soc. 142, 14417-14421 (2020).
“YTHDF2 Recognition of N1-methyladenosine (m1A)-modified RNA Is Associated with Transcript Destabilization” Seo, K. W.; Kleiner, R. E. ACS Chem. Biol. 15, 132-139 (2020).
“High-throughput approaches to profile protein-RNA interactions” Nechay, M.; Kleiner, R. E. Curr. Opin. Chem. Biol. 54, 37-44 (2019).
“In vitro selection with a site-specifically modified RNA library reveals the binding preferences of N6-methyladenosine (m6A) reader proteins” Arguello, A. E.; Leach, R. W.; Kleiner, R. E. Biochemistry 58, 3386-3395 (2019).
“A Metabolic Engineering Approach to Incorporate Modified Pyrimidine Nucleosides into Cellular RNA” Zhang, Y.; Kleiner, R. E. J. Am. Chem. Soc. 141, 3347-3351 (2019).
“A Photocrosslinking-Based RNA Chemical Proteomics Approach to Profile m6A-Regulated Protein-RNA Interactions” Arguello, A. E.; Srikumar, T.; Kleiner, R. E. Curr. Protoc. Nucleic Acid Chem. 75, e69 (2018).
“Reading the RNA Code” Kleiner, R. E. Biochemistry 57, 11-12 (2018).
“RNA Chemical Proteomics Reveals the N6-Methyladenosine (m6A)-Regulated Protein-RNA Interactome” Arguello, A. E.; DeLiberto, A. N.; Kleiner, R. E. J. Am. Chem. Soc. 139, 17249-17252 (2017).