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Computational Analysis of RNA modifications using Nanopore direct RNA sequencing

Supervisor: Dr Anton Enright
Based at the Division of Cellular Molecular Pathology, Tennis Court Road

enright1The rapid advance of high-throughput sequencing technologies has lead to the identification of specific post-transcriptional modifications in thousands of transcripts. These are derived for both protein-coding RNAs and other less abundant RNA classes. Biological functions for the vast majority of these modifications remain uncharacterised. However, many are expected to have significant structural impact. For instance, the well characterized N6-methyladenosine (m6A) modification has been shown to flag mRNAs for fast-track processing via m6A induced structural switches. Our laboratory is using novel technologies and methods to develop the next generation of approaches to the detection and understanding of RNA methylation. This project will involve the analysis of Oxford Nanopore RNA sequencing data with a view to developing novel basecalling algorithms which can delineate between methylated and unmethylated bases. Additionally, we will use this technology to explore the extent of RNA methylation across tissue types and disease states including cancer.

 

Recent publications

Ivanova I, Much C, Di Giacomo M, Azzi C, Morgan M, Moreira PN, Monahan J, Carrieri C, Enright AJ, O'Carroll D. Mol Cell. 2017 Aug 30. pii: S1097-2765(17)30577-4. doi: 10.1016/j.molcel.2017.08.003. The RNA m6A Reader YTHDF2 Is Essential for the Post-transcriptional Regulation of the Maternal Transcriptome and Oocyte Competence.  [Epub ahead of print]

Morgan M, Much C, DiGiacomo M, Azzi C, Ivanova I, Vitsios DM, Pistolic J, Collier P, Moreira PN, Benes V, Enright AJ, O'Carroll D. Nature. 2017 Aug 17;548(7667):347-351. doi: 10.1038/nature23318. mRNA 3' uridylation and poly(A) tail length sculpt the mammalian maternal transcriptome. Epub 2017 Aug 9.

Vitsios DM, Davis MP, van Dongen S, Enright AJ. Nucleic Acids Res. 2017 Feb 17;45(3):1079-1090. doi: 10.1093/nar/gkw1031. Large-scale analysis of microRNA expression, epi-transcriptomic features and biogenesis.