Back

Unraveling the Role of G-Quadruplexes in Alternative Polyadenylation (APA): A Focus on Neogenin 1

Lejault, P.; Bolduc, F.; Turcotte, M.-A.; Perreault, J. P.

2024-06-04 biochemistry
10.1101/2024.06.04.597383 bioRxiv
Show abstract

Polyadenylation is a crucial step in mRNA maturation. In half of the cases, alternative polyadenylation sites are used instead of canonical ones, affecting the length of the transcripts 3UTR. The mechanisms controlling the selection of these alternative polyadenylation sites are still unknown. Using a unique sequencing method (PolyAclick-seq) to identify different polyadenylated isoforms, we selected events modulated by RHPS4, a ligand known to stabilize G-quadruplex (G4). Through in silico selection, in vitro assays, and G4 mutagenesis construction, the pivotal role of rG4 structures in determining polyadenylation sites was uncovered, particularly for the gene encoding Neogenin-1 (NEO1). This research highlights the importance of focusing on G4 RNA mediated APA regulation in the 3UTR, as a method to alter isoform choice and impact protein synthesis opening up new avenues for RNA-based therapies.

Matching journals

The top 4 journals account for 50% of the predicted probability mass.

50% of probability mass above

"Similar papers" are the closest papers from that journal in the model's embedding space. They show what the match is built on, but the ranking comes mostly from a classifier over the whole training set, not from these examples alone.