RNA Modifications

Ribonucleic acid (RNA) has a breathtaking variety of biological functions, which far exceeds its classical role as a carrier of genetic information.  The repertoire of RNA is further diversified by covalent modifications that decorate all four canonical nucleotides in RNAs.

While methylation of the N6-position of adenosine (m6A) can have significant effects on RNA splicing, localization, translation and stability, the function(s) of the of the more than 140 other epitranscriptomic marks is largely unchartered territory. In RNA viruses, it was recently shown that these m6A-based epitranscriptomic marks regulate the nuclear export, expression, and stability of viral genomic RNA, establishing that RNA post-transcriptional modifications (PTMs) are key regulators of viral gene expression.

Using mass spectrometry, an unbiased and highly sensitive analytical approach, we discovered that the RNA genomes of Zika virus, Dengue virus, hepatitis C virus, poliovirus and human immunodeficiency virus are decorated with more than 30 different epitranscriptomic marks.  Using mass spectrometry, biochemical, molecular, and cell biological tools, and virology our long-term goal is to determine the regulatory importance of RNA modifications to cellular and viral RNAs following infection of RNA viruses.