RNA Chemical Proteomics Reveals the N-Methyladenosine (mA)-Regulated Protein-RNA Interactome.

TitleRNA Chemical Proteomics Reveals the N-Methyladenosine (mA)-Regulated Protein-RNA Interactome.
Publication TypeJournal Article
Year of Publication2017
AuthorsA Arguello, E, DeLiberto, AN, Kleiner, RE
JournalJ Am Chem Soc
Volume139
Issue48
Pagination17249-17252
Date Published2017 12 06
ISSN1520-5126
KeywordsAdenosine, AlkB Homolog 5, RNA Demethylase, Carrier Proteins, Cell Cycle Proteins, DNA Helicases, Fragile X Mental Retardation Protein, Humans, Neoplasm Proteins, Poly-ADP-Ribose Binding Proteins, Proteomics, RNA, RNA Helicases, RNA Recognition Motif Proteins, RNA-Binding Proteins, Ubiquitin Thiolesterase
Abstract

<p>Epitranscriptomic RNA modifications can regulate mRNA function; however, there is a major gap in our understanding of the biochemical mechanisms mediating their effects. Here, we develop a chemical proteomics approach relying upon photo-cross-linking with synthetic diazirine-containing RNA probes and quantitative proteomics to profile RNA-protein interactions regulated by N-methyladenosine (mA), the most abundant internal modification in eukaryotic RNA. In addition to identifying YTH domain-containing proteins and ALKBH5, known interactors of this modification, we find that FMR1 and LRPPRC, two proteins associated with human disease, "read" this modification. Surprisingly, we also find that mA disrupts RNA binding by the stress granule proteins G3BP1/2, USP10, CAPRIN1, and RBM42. Our work provides a general strategy for interrogating the interactome of RNA modifications and reveals the biochemical mechanisms underlying mA function in the cell.</p>

DOI10.1021/jacs.7b09213
Alternate JournalJ. Am. Chem. Soc.
PubMed ID29140688