Meeting Abstract
Post-transcriptional changes in RNA have the potential to influence the epigenetic landscape. As of today there are over a hundred RNA modifications. These chemical changes to nucleotides do not alter the sequence of RNA but can alter gene expression and has recently been described as part of a so-called epitranscriptome. Similar to DNA methylation, there are RNA methylation and demethylation enzymes. Methylation of adenosine to N6-methyladenine (m6A) is the most prevalent internal modification on mRNA and long non-coding RNA with up to 20% of the human mRNA routinely methylated. However, little is known about biological roles of RNA modifications. Here, we used the sea slug Aplysia, a prominent model organisms to study learning and memory, and chemically characterized the scope of the epitranscriptome focusing on the central nervous system and plasticity mechanisms. Using an ELISA, we determine that 4% of the total RNA was methylated in Aplysia. RNA-seq and computation analysis of the Aplysia genome shows that all the enzyme families involved in RNA methylation/demethylation are present in varying amounts from developmental states to single neurons. For the first time RNA modifications were identified and quantified in single neurons using ultrasensitive mass spectrometry (MS) in combination ultra-high performance liquid chromatography. Two different cholinergic neurons in Aplysia showed different and distinct RNA modifications. In addition to the RNA modification, we also discover cell- and tissue specific RNA editing in Aplysia. RNA editing is a process of targeted alterations of nucleotides in all types of RNA molecules. As a result, the transcriptional output differs from its genomic DNA template.
