Organisms live in highly variable environments where they regularly encounter perturbations such as heat, cold, or different environmental toxins. In response to these stressful conditions, organisms will often change the expression of genes that will help them to better maintain their function. This can be an important means of adaptation to variable environments. However, a much more flexible route for achieving this end would be a difference in the length of the 3’ untranslated region of the gene (a noncoding region of the gene’s transcript that is important for regulation, this is termed alternative polyadenylation). This does not require the time that de novo transcription takes, or a change in overall expression. Yet it can change gene expression but altering the stability of transcripts, their translation, or where they are sent in cells. This fellowship will address this question by investigating the role of the length of the 3’ untranslated region in Drosophila’s adaptation to ethanol. This fellowship will provide the Signor lab training and tools to conduct a method called 3’ sequencing, developed in our host lab at Memorial Sloan Kettering, to quantify alternative polyadenylation. Through this training this will address the following fellowship aims: i) enhance the research capabilities of the Signor lab ii) facilitate collaborations at NDSU and across other research networks (e.g. EPSCoR Track-2 ICE Network). The training in 3’ sequencing at Memorial Sloan Kettering will allow our group to test the hypothesis that alternative polyadenylation has been important for adaptation in Drosophila.
Gene expression differences between individuals and populations is important for differences in fitness. Yet, oftentimes mRNA expression differences do not result in different final phenotypes. Likewise, phenotypes can be linked to genes that do not show mRNA expression differences. What are the missing regulatory steps which result in these patterns, and how can we better understand the genotype to phenotype map? The failure of many studies to account for the possible influence of differences in mRNA processing may obfuscate some relationships between gene expression and phenotype, and could potentially be the key to understanding the next layer in the genotype to phenotype map. Our research will explicitly test for the importance of alternative polyadenylation in environmental response, using a classic model system, alcohol and Drosophila. Alternative polyadenylation can change where mRNA is localized, how it is exported from the nucleus, how long it is stable and whether or not it is translated. Very little is known about whether alternative polyadenylation is important for adaptation, particularly in response to the environment. Furthermore, we know very little about how alternative polyadenylation evolves between species and how it is regulated.
This award reflects NSF's statutory mission and has been deemed worthy of support through evaluation using the Foundation's intellectual merit and broader impacts review criteria.
