A critical assessment of the utility of protein-free splicing systems.
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In this article, the authors discuss the advances in both protein-free and fully spliceosomal systems that would be required to conclude that the reactions observed to be catalyzed by protein free snRNAs are related to splicing and question the reliability of snRNA-only systems as tools for mechanistic splicing research.Abstract:
U2 and U6 snRNAs form part of the catalytic spliceosome and represent strong candidates for components of its active site. Over the past decade it has become clear that these snRNAs are capable of catalyzing several different chemical reactions, leading to the widespread conclusion that the spliceosome is a ribozyme. Here, we discuss the advances in both protein-free and fully spliceosomal systems that would be required to conclude that the reactions observed to be catalyzed by protein-free snRNAs are related to splicing and question the reliability of snRNA-only systems as tools for mechanistic splicing research.read more
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References
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Journal ArticleDOI
Pre-mRNA Splicing: Awash in a Sea of Proteins
TL;DR: The number of new proteins emerging with no prior connection to splicing was surprising and it would be premature to label these proteins as bona fide splicing factors, yet many were identified multiple times in complexes purified under diverse conditions or from different organisms.
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Crystal structure of a self-spliced group II intron.
TL;DR: Structural and functional analogies support the hypothesis that group II introns and the spliceosome share a common ancestor.
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Splicing-related catalysis by protein-free snRNAs
Saba Valadkhan,James L. Manley +1 more
TL;DR: It is shown that a protein-free complex of two snRNAs, U2 and U6, can bind and position a small RNA containing the sequence of the intron branch site, and activate the branch adenosine to attack a catalytically critical domain of U6 in a reaction that is related to the first step of splicing.
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"Nought may endure but mutability": spliceosome dynamics and the regulation of splicing.
TL;DR: The spliceosome is both compositionally and conformationally dynamic, allowing splice site choice to be regulated throughout both the assembly and catalytic phases of the reaction.
Journal ArticleDOI
Metal ion catalysis during group II intron self-splicing: parallels with the spliceosome.
TL;DR: It is shown that 3'-sulfur substitution at the 5' splice site of a group II intron causes a metal specificity switch during the first step of splicing, and striking parallels between the catalytic mechanisms employed by these two systems are provided.