About me
Following my BSc in Biological Sciences, I obtained an MSc in Infection, Immunity, and Human Disease at the University of Leeds to further develop my areas of interest and expand my knowledge and understanding of virus-host cell interactions. During my MSc, I undertook an extended research project based on the effect of post-transcriptional modifications on Chikungunya virus replication within mosquito host cells. I expanded both my repertoire of key scientific techniques, and pursued my passion for virus-host interactions, particularly RNA processing events, by working as a research assistant for a year in a cancer virology lab. These research positions confirmed my desire to establish a career in research, leading me to pursue a PhD.
My Project
N⁶-Methyladenosine (m⁶A) is the most abundant modification of eukaryotic mRNA, consisting of the addition of a methyl group to adenosine at conserved DRACH consensus sequences. The m⁶A machinery comprises three main groups: methyltransferases (writers) which add the modification; RNA-binding proteins (readers) which recognise and bind to the modified transcript, directing it towards its distinct biological fate; and demethylases (erasers), which reverse the modification. Since its discovery, m⁶A has been associated with every stage of mRNA metabolism, playing important roles in splicing, nuclear export, translation modulation, stability and mRNA decay. Consequently, m⁶A plays key roles in regulatory control within various physiological pathways and not surprisingly has been implicated in the life cycle of multiple viruses. Kaposi’s Sarcoma-associated herpesvirus (KSHV) is associated with multiple malignancies and like all herpesviruses, has a biphasic lifecycle, consisting of two distinct phases: a lytic replicative phase, and a persistent latent state. The KSHV transcriptome is heavily m⁶A-methylated during lytic replication, and this is essential for efficient virus replication and infectious virion production. Recent work identified several members from the ‘Royal family’ of RNA-binding proteins as putative m⁶A readers of KSHV m⁶A-methylated mRNAs. These include SND1, which binds to and stabilises the viral ORF50 mRNA. However, we believe other Royal proteins bind alternative viral m⁶A-methylated transcripts, suggesting they may be involved at different temporal stages of replication. My project aims to elucidate the roles and importance of various Royal proteins within KSHV lytic replication, furthermore, we will elucidate how and why different reader proteins have specificity towards certain viral m⁶A-methylated transcripts.
Connect
LinkedIn: https://www.linkedin.com/in/sarah-menezes-6265491a4/