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Structural biology of poly(A) site definition
1Department of Microbiology and Molecular Genetics, University of Vermont, Burlington, USA.
Wiley Interdisciplinary Reviews. RNA
|August 9, 2011
Summary
Messenger RNA (mRNA) 3' processing involves cleavage and polyadenylation, crucial for maturation. This review details how sequence elements and protein factors interact to select the poly(A) site in eukaryotes.
Area of Science:
- Molecular Biology
- RNA Biology
- Biochemistry
Background:
- Messenger RNA (mRNA) maturation requires 3' processing, a two-step reaction involving endonucleolytic cleavage and polyadenylation.
- Metazoan histone mRNAs are an exception, undergoing cleavage but not polyadenylation.
- Poly(A) site recognition depends on mRNA 3' untranslated region (UTR) sequence elements and associated protein factors.
Purpose of the Study:
- To review the interactions between mRNA cis-elements and protein factors that define the poly(A) site.
- To elucidate the mechanisms of sequence recognition in mRNA 3' processing.
- To highlight the role of protein factors in poly(A) site selection and machinery assembly.
Main Methods:
- Focus on interactions between mRNA cis-elements and protein factors.
- Review of structural studies of protein-RNA complexes.
- Comparative analysis of factors in mammalian cells and yeast (Saccharomyces cerevisiae).
Main Results:
- In mammals, UGUA, AAUAAA, and GU-rich elements are recognized by cleavage factor I(m) (CFI(m)), cleavage and polyadenylation specificity factor (CPSF), and cleavage stimulation factor (CstF), respectively.
- In yeast, UA repeats and A-rich elements are recognized by Hrp1p and cleavage factor IA.
- Structural studies reveal mechanisms of sequence recognition and protein factor roles in poly(A) site selection.
Conclusions:
- Protein-RNA interactions are central to defining the poly(A) site during mRNA 3' processing.
- Understanding these interactions is key to deciphering the assembly of the 3' processing machinery.
- This review synthesizes current knowledge on cis-elements and protein factors involved in eukaryotic poly(A) site selection.
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