Ralph Kleiner
Contact
rkleiner@princeton.eduResearch Area
Biochemistry, Biophysics & Structural BiologyResearch Focus
Chemistry of cellular RNAOur 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.
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. Chemical Method to Sequence 5-Formylcytosine on RNA. ACS Chem Biol. 2022 ;17(3):503-508.
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. Reactivity-dependent profiling of RNA 5-methylcytidine dioxygenases. Nat Commun. 2022 ;13(1):4176.
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. Live-Cell RNA Imaging with Metabolically Incorporated Fluorescent Nucleosides. J Am Chem Soc. 2022 ;144(32):14647-14656.
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. Activity-based RNA-modifying enzyme probing reveals DUS3L-mediated dihydrouridylation. Nat Chem Biol. 2021 ;17(11):1178-1187.
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. Publisher Correction: A neural mA/Ythdf pathway is required for learning and memory in Drosophila. Nat Commun. 2021 ;12(1):1743.
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. A neural mA/Ythdf pathway is required for learning and memory in Drosophila. Nat Commun. 2021 ;12(1):1458.
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. Mechanisms of epitranscriptomic gene regulation. Biopolymers. 2021 ;112(1):e23403.
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. Interrogating the transcriptome with metabolically incorporated ribonucleosides. Mol Omics. 2021 ;17(6):833-841.
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. YTHDF2 Recognition of N-Methyladenosine (mA)-Modified RNA Is Associated with Transcript Destabilization. ACS Chem Biol. 2020 ;15(1):132-139.
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. High-throughput approaches to profile RNA-protein interactions. Curr Opin Chem Biol. 2020 ;54:37-44.
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. Cell- and Polymerase-Selective Metabolic Labeling of Cellular RNA with 2'-Azidocytidine. J Am Chem Soc. 2020 ;142(34):14417-14421.
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. The Parkinson's disease e-diary: Developing a clinical and research tool for the digital age. Mov Disord. 2019 ;34(5):676-681.
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. A Metabolic Engineering Approach to Incorporate Modified Pyrimidine Nucleosides into Cellular RNA. J Am Chem Soc. 2019 ;141(8):3347-3351.
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. Selection with a Site-Specifically Modified RNA Library Reveals the Binding Preferences of N-Methyladenosine Reader Proteins. Biochemistry. 2019 ;58(31):3386-3395.
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. Reading the RNA Code. Biochemistry. 2018 ;57(1):11-12.
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. A Photocrosslinking-Based RNA Chemical Proteomics Approach to Profile m A-Regulated Protein-RNA Interactions. Curr Protoc Nucleic Acid Chem. 2018 ;75(1):e69.
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. RNA Chemical Proteomics Reveals the N-Methyladenosine (mA)-Regulated Protein-RNA Interactome. J Am Chem Soc. 2017 ;139(48):17249-17252.
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. An intein-based genetic selection allows the construction of a high-quality library of binary patterned de novo protein sequences. Protein Eng Des Sel. 2005 ;18(4):201-7.