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Analysis of RNA Processing Reactions Using Cell Free Systems: 3' End Cleavage of Pre-mRNA Substrates in vitro
Published on: May 3, 2014
RNA-binding proteins in regulation of alternative cleavage and polyadenylation
1Department of Biochemistry and Molecular Biology, University of Medicine and Dentistry of New Jersey (UMDNJ)-New Jersey Medical School, 185 South Orange Ave., Newark, NJ, 07103, USA.
Abstract:
Almost all eukaryotic pre-mRNAs are processed at the 3' end by the cleavage and polyadenylation (C/P) reaction, which preludes termination of transcription and gives rise to the poly(A) tail of mature mRNA. Genomic studies in recent years have indicated that most eukaryotic mRNA genes have multiple cleavage and polyadenylation sites (pAs), leading to alternative cleavage and polyadenylation (APA) products. APA isoforms generally differ in their 3' untranslated regions (3' UTRs), but can also have different coding sequences (CDSs). APA expands the repertoire of transcripts expressed from the genome, and is highly regulated under various physiological and pathological conditions. Growing lines of evidence have shown that RNA-binding proteins (RBPs) play important roles in regulation of APA. Some RBPs are part of the machinery for C/P; others influence pA choice through binding to adjacent regions. In this chapter, we review cis elements and trans factors involved in C/P, the significance of APA, and increasingly elucidated roles of RBPs in APA regulation. We also discuss analysis of APA using transcriptome-wide techniques as well as molecular biology approaches.
Insights
Alternative cleavage and polyadenylation (APA) generates diverse mRNA isoforms by utilizing multiple polyadenylation sites. RNA-binding proteins (RBPs) are key regulators of this crucial gene expression process.
Area of Science:
- Molecular Biology
- Genetics
- Biochemistry
Background:
- Eukaryotic pre-mRNA 3' end processing involves cleavage and polyadenylation (C/P).
- Most eukaryotic mRNA genes possess multiple cleavage and polyadenylation sites (pAs), resulting in alternative cleavage and polyadenylation (APA) products.
- APA isoforms can differ in 3' untranslated regions (3' UTRs) or coding sequences (CDSs), expanding transcript diversity.
Purpose of the Study:
- To review cis elements and trans factors in C/P.
- To highlight the significance of APA in gene expression regulation.
- To elucidate the roles of RNA-binding proteins (RBPs) in regulating APA.
Main Methods:
- Review of genomic studies and existing literature.
- Discussion of transcriptome-wide techniques for APA analysis.
- Consideration of molecular biology approaches for studying APA.
Main Results:
- APA is a highly regulated process under various physiological and pathological conditions.
- RNA-binding proteins (RBPs) are critical regulators of APA.
- RBPs function either as part of the C/P machinery or by influencing pA site selection through binding to regulatory regions.
Conclusions:
- APA significantly expands the transcriptome's complexity.
- RBPs play pivotal roles in controlling APA.
- Understanding APA mechanisms is crucial for comprehending gene expression regulation and its implications in disease.
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