Abstract The control of organellar gene expression is critical for cellular programming of all eukaryotic organisms. While perturbing mitochondrial gene expression leads to human pathologies, including cancer, altering plastidial gene expression can kill plants. However, the cell signaling mechanisms that control organellar gene expression remain poorly understood. The long-term goal of the PI’s laboratory is to utilize photoreceptor-regulated chloroplast biogenesis in Arabidopsis as a genetic model to understand cell signaling mechanisms controlling organellar gene expression. The current data support the central hypothesis that the red and far-red photoreceptors, the phytochromes, induce the expression of plastid- encoded photosynthesis-associated genes through nucleus-to-plastid signaling that activates a bacterial- type plastidial RNA polymerase. Here the PI propose to utilize a combination of molecular genetics, biochemistry, structure biology, cell biology, and genomics approaches to (1) determine the activation mechanism of the bacterial-type RNA polymerase in plastids, (2) identify the nucleus-to-plastid signal that triggers the activation of the plastidial RNA polymerase, and (3) determine the phytochrome signaling mechanism that initiates the nucleus-to-plastid signaling in the nucleus. The proposed research is innovative because it utilizes photoreceptor signaling and chloroplast biogenesis in Arabidopsis as a genetic model to investigate a previously uncharacterized nucleus-to-organelle signaling pathway. The PI has developed new forward genetic screens and biochemical assays to identify components in the nucleus-to-plastid signaling and elucidate their signaling mechanisms. The proposed research is significant, because it is expected to uncover the photoreceptor signaling mechanisms controlling plastidial transcription - a long-standing gap in our knowledge of plant light signaling and chloroplast biogenesis. Because the control of transcription in plastids shares many similarities with that in mitochondria, what we learn in the plastid model is expected to enhance the understanding of the general principles of cell signaling mechanisms in controlling organellar gene expression, including the regulation of mitochondrial gene expression, and therefore, will ultimately contribute to the understanding of the mechanisms underlying the misregulations of mitochondrial gene expression in human diseases.

Project Narrative The proposed research is relevant to public health because the discovery of the basic regulatory mechanisms of organellar gene expression is ultimately expected to increase understanding of how misregulations of mitochondrial gene expression lead to human diseases such as cancer. Thus, the proposed research is relevant to the part of NIH’s mission that pertains to developing fundamental knowledge that will help to reduce the burdens of human disability.