Gonzalez Figueroa, Carlos
Mentor: Dr. Grace Xiao
Recent advances in next-generation sequencing have facilitated identification of millions of RNA editing sites. It is increasingly recognized that many diseases, such as neurological disorders and cancer, manifest global changes in RNA editing. Adenosine deaminase acting on RNA (ADAR) proteins are a family of RNA binding proteins that play a key role in RNA editing. The functional roles and regulatory mechanisms of RNA editing in health and disease are poorly understood. In several disease states, ADAR expression levels are similar to the normal state, but editing levels are significantly altered. Therefore, identifying additional proteins and mechanisms that regulate ADAR activity and RNA editing is of profound importance. We are interested in the regulation and function of RNA editing in the context of two RNA binding proteins: HuR and hnRNPM.
HuR, was shown to interact with ADAR and cooperatively regulate RNA stability. However, whether this regulation is editing-dependent was not investigated. We hypothesize that editing-dependent mRNA stabilization is a general mechanism affecting many genes. Thus, stabilizing edited mRNAs (or destabilizing unedited mRNAs) could be a critical mechanism to control dsRNA content in the cytoplasm. On the other hand, in a preliminary study of regulatory proteins of RNA editing, we unexpectedly observed that hnRNP M knockdown (KD) induced significant up-regulation of RNA editing in multiple cell types. Thus, hnRNP M may directly or indirectly regulate RNA editing. My research aims to achieve a better understanding of the basic mechanisms of regulation and function of RNA editing, using a combination of genomic, bioinformatic and molecular biology approaches.
