Alternative polyadenylation in development and disease

The various regulatory functions of the non-coding genome have become increasingly clear in the past decade. In particular, alternative polyadenylation (APA) is a co-transcriptional gene regulatory mechanism by which the cell can produce alternative mRNA isoforms with different polyadenylation sites, often but not always located in the 3’ UTR. Since the 3’ UTR contains regulatory signals, including binding sites for microRNAs and RNA-binding proteins, different isoforms, while often coding for identical proteins, can show functionally significant differences in terms of stability, cellular localization, translational efficiency, and even protein-protein interactions. Patterns of APA have been shown to be tissue-specific and to be regulated during development and in physiological responses to stimuli; their dysregulation has been associated to both cancer and complex diseases. However, much remains to be understood about the mechanisms leading to APA, its functional consequences in physiological and pathological contexts, its evolutionary history, and its patterns of variation among individuals and among single cells.

This Research Topic aims to cover recent advances, including methodological ones, in the understanding of the mechanisms and consequences of APA and its dysregulation in disease, by providing new insight on questions such as:

· The interplay of genetic, epigenetic, and environmental factors in the regulation of APA
· The mechanisms of APA dysregulation in cancer and its functional relevance
· The inter-individual variation of APA, its genetic determinants, and its relevance to complex traits
· The inter-cell variation of APA in development and disease
· The evolution of APA and its adaptive significance

This Research Topic will include several types of contributions, including but not limited to:

· Advances in experimental techniques for the assessment of APA
· Advances in computational techniques for the study of APA from existing -omics datasets
· Genome-wide investigations of APA mechanisms and functional relevance in developmental, physiological, or pathological contexts
· Comparative genomics of APA aimed at understanding its evolutionary history and significance
· Single cell assays or data analysis aimed at understanding inter-cell heterogeneity of APA in cancer and development and the associated mechanisms and functional consequences
· In depth experimental studies of APA in specific genes and developmental, physiological, and pathological contexts