Alternative Polyadenylation: a new frontier in post transcriptional regulation

Fanggang Ren,Lan Zhang,Na Zhang,Eric Miller,Jeffrey J Pu

doi:10.1186/s40364-020-00249-6

Abstract

Polyadenylation of pre-messenger RNA (pre-mRNA) specific sites and termination of their downstream transcriptions are signaled by unique sequence motif structures such as AAUAAA and its auxiliary elements. Alternative polyadenylation (APA) is an important post-transcriptional regulatory mechanism that processes RNA products depending on its 3′-untranslated region (3′-UTR) specific sequence signal. APA processing can generate several mRNA isoforms from a single gene, which may have different biological functions on their target gene. As a result, cellular genomic stability, proliferation capability, and transformation feasibility could all be affected. Furthermore, APA modulation regulates disease initiation and progression. APA status could potentially act as a biomarker for disease diagnosis, severity stratification, and prognosis forecast. While the advance of modern throughout technologies, such as next generation-sequencing (NGS) and single-cell sequencing techniques, have enriched our knowledge about APA, much of APA biological process is unknown and pending for further investigation. Herein, we review the current knowledge on APA and how its regulatory complex factors (CFI/IIm, CPSF, CSTF, and RBPs) work together to determine RNA splicing location, cell cycle velocity, microRNA processing, and oncogenesis regulation. We also discuss various APA experiment strategies and the future direction of APA research.

Highlights

Splicing, capping, and polyadenylation are three major steps in processing pre-messenger RNA to mRNA [1, 2]
RNA-binding proteins (RBPs) can work alone to prevent the binding of other Alternative polyadenylation (APA) factors to the proximal poly(A) sites or affect APA selection through its role in maintaining RNA stability [53,54,55]
By analyzing 515 scRNA-seq datasets extracted from 11 breast cancer patients, Kim et al reported that cell-type-specific APA can be identified in single cell level based on 3′-untranslated region (3′-UTR) length variation in combination with gene expression level and APA patterns

Summary

Introduction

Splicing, capping, and polyadenylation are three major steps in processing pre-messenger RNA (pre-mRNA) to mRNA [1, 2]. This provides sequence specificity that may play an important role in regulating pA site selection, gene expression, cancer cell migration, metastasis, and eventually disease outcome [32].

Results

Conclusion