Abstract
Post-transcriptional processing, involving cleavage of precursor messenger RNA (pre mRNA), and further incorporation of poly(A) tail to the 3' end is a key step in the expression of genetic information. Alternative polyadenylation (APA) serves as an important check point for the regulation of gene expression. Recent studies have shown widespread prevalence of APA in diverse systems. A considerable amount of research has been done in characterizing different subunits of so-called Cleavage and Polyadenylation Specificity Factor (CPSF). In plants, CPSF30, an ortholog of the 30 kD subunit of mammalian CPSF is a key polyadenylation factor. CPSF30 in the model plant Arabidopsis thaliana was reported to possess unique biochemical properties. It was also demonstrated that poly(A) site choice in a vast majority of genes in Arabidopsis are CPSF30 dependent, suggesting a pivotal role of this gene in APA and subsequent regulation of gene expression. There are also indications of this gene being involved in oxidative stress and defense responses and in cellular signaling, suggesting a role of CPSF30 in connecting physiological processes and APA. This review will summarize the biochemical features of CPSF30, its role in regulating APA, and possible links with cellular signaling and stress response modules.
Highlights
The formation of the mature 3' end of mRNA in the nucleus is a key step in gene expression in all eukaryotes
Over-expression of CPSF30 in lung cancer cells results in activation of human telomerase reverse transcriptase, which was shown to be associated with the proliferation of cancer cells [65,66]. These findings suggest that altering the activity of CPSF30 in different cellular settings may lead to large scale reprogramming of gene expression, and show that interactions with other regulatory factors (NS1) can alter the activity and function of CPSF30 in vivo
Stress-responsive genes are over-represented in the set of genes that possess AtCPSF30-dependent poly(A) sites that lie within 5'-UTRs, protein-coding regions, and introns. Usage of such sites is likely to alter the expression and/or function of the associated gene; this correlation is suggestive of a role for AtCPSF30-mediated Alternative polyadenylation (APA) in the regulation of expression of genes involved in stress responses
Summary
The formation of the mature 3' end of mRNA in the nucleus is a key step in gene expression in all eukaryotes. Stress and developmental cues can initiate cellular signaling transmitted through redox and/or calcium-calmodulin mediated signaling cascade, altering RNA binding and/or endonuclease activities of AtCPSF30 This leads to global changes in poly(A) site choice, resulting in numerous biochemical and molecular consequences (induction of protein quality control system, as well as alteration of mRNA stability, translatability and localization). This study reported several novel phenotypes in an Arabidopsis mutant (termed oxt6) bearing a T-DNA insertion within the first exon of the At1g30460 locus; this mutant is a null, and produces neither the small AtCPSF30 polypeptide nor the larger CPSF30-YTH protein encoded by this locus [51] These phenotypes include lower fertility, reduced lateral root formation, altered responses to plant growth regulators, and modified sensitivity to oxidative stress.
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