MSc Graduate Seminar-Noa Shimon
15/08/2022 13:00

Studying the functionalsignificance of RNA editing and duplicated genomic regions in Caenorhabditiselegans

RNAediting is a phenomenon of RNA sequence alteration after transcription ineukaryotes. In mammals, the most common alterations studied are -Adenosine-to-Inosine (A-to-I editing) and Cytidine-to-Uridine (C-to-U editing).A-to-I RNA editing is catalyzed by the conserved ADAR (Adenosine Deaminasesthat Act on RNA) members on dsRNAs. To date, in C. elegans, only thistype of editing has been demonstrated. The second alteration – C-to-U editing-is known to be catalyzed by the APOBEC (ApolipoProtein B mRNA Editing enzyme,Catalytic polypeptide) family in mammals within ssDNA and RNA. Our lab hasrecently found that the protein-coding gene with an unknown function ZK287.1(termed abec-1) in C. elegans is homologous to the human APOBECfamily, both in sequence and structure. Therefore, we looked for C-to-U editingin the nematode. We could not detect C-to-U RNA editing and have indicationsthat C-to-U editing on DNA does not occur as well. However, in worms lackingZK287.1, we observed expression and editing changes in A-to-I edited genes,indicating a possible function of ZK287.1 on A-to-I RNA editing process.

We alsostudied how wide the gene duplication phenomena is in C. elegans and itspurpose. Therefore, we built a computational pipeline to identify duplications.We found 242 different genes or pseudogenes that have duplications, identicalin sequence. We hypothesized that the duplicated pairs regulate the expressionof each other via the generation of dsRNA, whichis recognized by the RNAi pathway and A-to-I RNA editing. Studying A-to-I RNAediting, we found that 24% of the genes with duplications are edited,which is highly significant. Furthermore, our analysis of siRNA-sequencing dataof wildtype C. elegans worms and ADAR mutant worms (adr-1(tm668) I; adr-2 (ok735) III), at two different developmental stages,revealed that siRNAs targeting the genes with duplications are significantlyupregulated in the ADAR mutant worms, similarly to the pattern exhibitedby A-to-I edited genes. Surprisingly, our analyses of RNA-sequencing dataof the same worm strains did not detect downregulation of the genes withduplications, as observed in edited genes. Thus, possibly duplicated genes aretargeted by ADAR proteins; however, we still do not know if this editingaffects the regulation of expression or function and how.