Pavla Brachova, PhD
Research Assistant Professor
Molecular and Integrative Physiology
PhD, University of Iowa
Recent technology advancements have led to a boom in the number of known RNA modifications. Currently, over 100 known RNA modifications are known, such as N6-methyladenosine (m6A) and adenosine to inosine (A-to-I) deamination. Each modification can affect RNA structure, export, splicing, and RNA stability. Understanding the function of each of these, as well as their dynamic interplay is an exciting and novel area of study. Moving beyond descriptive studies is essential, and the oocyte is a model in which it is possible to examine function and mechanism, and also physiology. My research aims to understand the role of RNA modifications in oocyte developmental competence.
Our resent work in mouse GV oocytes and MII eggs shows that inosine RNA edits are a common RNA modification. We discovered inosine RNA editing occurs in gene coding regions, and is enriched at the codon wobble position. This is an important observation that has not been reported before. Deamination of adenosine to inosine at the wobble position changes the base pairing properties of the codon with the anticodon of transfer RNA (tRNA). For example, the AAA codon is bound by the tRNA anticodon TTT. Deamination of the wobble position of the AAA codon generates a new codon, AAI, which is bound by the tRNA anticodon TTC. Inosine modifications at the wobble position can therefore alter the codon composition of mRNA, potentially altering codon optimality. Codon optimality is a phenomenon in which specific codons associated with increased mRNA stability are considered optimal, while codons associated with decreased stability are considered non-optimal. Non-optimal codons can slow translation, impact translation elongation rates, and decrease mRNA half-life. Codon optimality depends on the balance between the concentration of tRNA available (tRNA supply) and the frequency of codon occurrence in the expressed mRNA (tRNA demand). Therefore, based on the speed of ribosome movement along the transcript, codon optimality can affect both translation rates and mRNA stability. During the maternal to zygotic transition, translation and degradation of maternal mRNA are coupled, and are necessary for successful embryonic development. We hypothesis is inosine impacts codon optimality, which affects translational efficiency and subsequently maternal mRNA degradation during MZT. This work has important implications for our understanding of A-to-I RNA editing and maternal mRNA decay, mechanisms essential for the generation of high quality oocytes.
Last modified: Apr 02, 2019