Alternative Polyadenylation: a new frontier in post transcriptional regulation
- PDF / 1,554,054 Bytes
- 10 Pages / 595.276 x 790.866 pts Page_size
- 46 Downloads / 191 Views
REVIEW
Open Access
Alternative Polyadenylation: a new frontier in post transcriptional regulation Fanggang Ren1,2, Na Zhang1,2, Lan Zhang1,2, Eric Miller1 and Jeffrey J. Pu1*
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.
Introduction Splicing, capping, and polyadenylation are three major steps in processing pre-messenger RNA (pre-mRNA) to mRNA [1, 2]. Polyadenylation (poly(A)) involves in endonucleolytic cleavage of pre-mRNA and addition of the poly(A) tail at the cleavage site [1]. Individual premRNA usually harbors a few cleavage/polyadenylation (C/P) sites (polyA sites or pA) [2]. Alternative polyadenylation (APA) can eventually produce several mRNA polyadenylation isoforms [3]. According to current understanding, APA is a comprehensive process accomplished via coordinative actions of several small molecules. The 3′-processing factors are the major targets of APA regulation [4]. Typical APA processing includes the following steps: (1) * Correspondence: [email protected]; [email protected] 1 Upstate Cancer Center, State University Of New York Upstate Medical University, Suite 331, CWB, 750 E. Adams Street, Syracuse, NY 13210, USA Full list of author information is available at the end of the article
CFIm (cleavage factor I) binds to the UGUA field of premRNA upstream of the pA site and attracts CPSF (cleavage and polyadenylation specificity factor) and CSTF (cleavage stimulation factor) to assemble at the end of RNA polymerase II; (2) as RNA polymerase II advances, CPSF binds to the pA signal sequence (e.g. AAUAAA) and CSTF is transferred to the new mRNA precursor, binding to the GU or U-rich sequence; (3) CPSF and CSTF initiate the cl
Data Loading...
