polyadenylation
Definition
Polyadenylation is a post-transcriptional modification process where a poly(A) tail—a sequence of approximately 200-250 adenine nucleotides—is added to the 3' end of newly transcribed mRNA molecules. This process occurs in the nucleus and is essential for mRNA stability, nuclear export, translation efficiency, and regulation of gene expression. Polyadenylation involves cleavage of the pre-mRNA at specific polyadenylation signals (typically AAUAAA hexanucleotide sequences) followed by addition of the poly(A) tail by poly(A) polymerase. Alternative polyadenylation (APA) allows a single gene to produce multiple mRNA isoforms with different 3' UTR lengths, affecting mRNA localization, stability, and protein output. Dysregulation of polyadenylation is implicated in cancer, neurological disorders, and other diseases, making it a critical regulatory mechanism in transcriptomics research.
Visualize polyadenylation in Nodes Bio
Researchers can use Nodes Bio to visualize networks connecting genes undergoing alternative polyadenylation with their regulatory factors, including cleavage and polyadenylation specificity factors (CPSF), cleavage stimulation factors (CstF), and RNA-binding proteins. Network analysis can reveal how polyadenylation site selection influences downstream pathways, identify co-regulated gene clusters sharing similar polyadenylation patterns, and map causal relationships between polyadenylation machinery components and disease phenotypes across different tissue types or experimental conditions.
Visualization Ideas:
- Gene regulatory networks showing polyadenylation factor interactions with target mRNAs and downstream effects on protein expression
- Alternative polyadenylation site usage networks comparing different cell types, disease states, or developmental stages
- Causal networks linking polyadenylation machinery mutations to changes in mRNA isoform abundance and phenotypic outcomes
Example Use Case
A cancer research team investigating tumor progression discovers that oncogenes in aggressive breast cancer cells preferentially use proximal polyadenylation sites, producing mRNA isoforms with shorter 3' UTRs that escape microRNA-mediated repression. Using transcriptomics data from patient samples, they identify a network of genes showing coordinated alternative polyadenylation shifts. By mapping these genes alongside their interacting RNA-binding proteins and affected signaling pathways, researchers uncover that CFIm25 downregulation drives widespread 3' UTR shortening, leading to increased oncogene expression and identifying potential therapeutic targets for restoring normal polyadenylation patterns.