Poster abstracts
Poster number 85 submitted by Emma Lamb
Defining a co-regulatory relationship between RNA binding proteins ADR-2 and TDP-1 in C. elegans nervous systems
Emma Lamb (Indiana University Department of Biology), Heather Hundley (Indiana University Department of Biology )
Abstract:
Editing of RNA not only contributes to molecular diversity of transcripts within a cell, but also mediates RNA silencing, innate immune activation, and numerous developmental processes (Erdmann et al., 2021). ADARs (Adenosine Deaminases that Act on RNA) are enzymes that bind double-stranded RNA catalyzing the deamination of adenosine to inosine (A-to-I editing). As RNA polymerase II is polymerizing a transcript, the nascent RNA can act as a binding site for proteins like ADARs that bind dsRNA (Yu et al., 2023). One such RNA binding protein is the human ortholog TAR-DNA binding protein, TDP-1. This protein binds RNA and promotes its nuclear localization for several processes including small RNA degradation pathways, translation, and stress granule formation. The loss of TDP-1 promotes ADAR editing of intron-containing regions of RNA by repressing cytoplasmic localization of dsRNA (Saldi et al. 2014). RNA sequencing data comparing first larval stage worms and mature worms indicated that in neurons there is a shift in the targets of A-to-I editing from mostly 3’ UTRs to mostly introns (Rajendran 2021). This is of interest as the activity of ADARs has been linked to neurological phenotypes in mammals as well as C. elegans such as impaired chemotaxis capability and motor coordination (Yang et al., 2021). These findings pose further questions about the implications of TDP-1 antagonism of the intronic editing by ADARs in neuronal health and development which would inform the work connecting both ADAR and TDP-1 activity to human neurodegenerative diseases like Alzheimer’s Disease and ALS. Here, I detail my plans to address these questions over the course of my degree.
References:
Erdmann, E. A. et al. (2021). To protect and modify double-stranded RNA – the critical roles of ADARs in development, immunity, and oncogenesis. Critical Reviews in Biochemistry and Molecular Biology, 56(1), 54–87.
Rajendren, S. et al. (2021). Profiling neural editomes reveals a molecular mechanism to regulate RNA editing during development. Genome
Research, 31(1), 27–39.
Saldi, T. K. et al. (2014). TDP-1, the Caenorhabditis elegans ortholog of TDP-43, limits the accumulation of double-stranded RNA. The EMBO Journal, 33(24),
2947–2966.
Yu, G. et al. (2023).Genome-wide probing of eukaryotic nascent RNA structure elucidates cotranscriptional folding and its antimutagenic effect. Nature Communications, 14(1), 5853.
Keywords: ADAR, neuron, RBP