Eva Maria Novoa
Accurate detection of m6A RNA modifications in native RNA sequences using third-generation sequencing
About Eva Maria Novoa
Eva Maria Novoa obtained her BSc in Biochemistry in 2007 with Honours, followed by an MSc in Bioinformatics in 2009. Since then, she has conducted research across three continents, including the Institute for Research in Biomedicine (IRB Barcelona) in Spain, the Massachusetts Institute of Technology and the Broad Institute in the USA, and the Garvan Institute of Medical Research in Australia. During these years, she has generated a substantial research profile in the field of protein translation and post-transcriptional regulation, using a combination of molecular biology, biochemistry and bioinformatic approaches. Since 2018, she has been Group Leader at the Center for Genomic Regulation (CRG) in Spain, in a dual appointment with the Garvan Institute, where she leads a team of 8 people. Her current work is focused on deciphering the language of RNA modifications, and how its orchestration can regulate our cells in a space-, time- and signal-dependent manner. Eva has received fellowships from EMBO, HFSP, “LaCaixa” and the ARC, and her work has been awarded with the Fisher Scientific Prize for Young Researchers (2013) given by the Spanish Society of Molecular Biology and Biochemistry, and the Young Researcher Award (2016) given by the Catalan Society of Biology.
From the battery of over 170 known RNA modifications, more than 70 have already been linked to human diseases, including neurological disorders and cancer, highlighting their importance in proper cellular functioning. Unfortunately, the limited availability of antibodies and chemicals selective to RNA modifications has so far limited our transcriptome-wide view to only a handful of RNA modifications. Consequently, the abundance, location, and function of the majority of RNA modifications remains unknown. To overcome these limitations, we have employed direct RNA sequencing from Oxford Nanopore Technologies, which allows direct sequencing of native RNA molecules, without any further amplification or reverse transcription step, thus potentially allowing for direct detection of RNA modifications in the full-length RNA transcripts. Using this technology, we have trained an algorithm that allows for the detection m6A RNA modifications in a quantitative manner and with single nucleotide resolution, finding that we can detect m6A RNA modifications with an overall accuracy of 90%. We then validate our findings in vivo, showing that our methodology can detect m6A modifications in yeast. As a control, we show that these modifications are not predicted by our algorithm in Ime4 knockout strains, which lack m6A. Our results open new avenues to investigate the universe of RNA modifications in full-length transcripts, with single molecule resolution. The establishment of the Oxford Nanopore platform as a tool to map virtually any given modification will allow us to query the epitranscriptome in ways that, until now, had not been possible. Future work can expand to other modifications like 5-methylcytosine (m5C), as well as provide additional thresholds for controlling specificity and sensitivity.
Eva Maria Novoa