Publication Date:
2014-09-26
Description:
The formation of branched lariat RNA is an evolutionarily conserved feature of splicing reactions for both group II and spliceosomal introns. The lariat is important for the fidelity of 5' splice-site selection and consists of a 2'-5' phosphodiester bond between a bulged adenosine and the 5' end of the intron. To gain insight into this ubiquitous intramolecular linkage, we determined the crystal structure of a eukaryotic group IIB intron in the lariat form at 3.7 A. This revealed that two tandem tetraloop-receptor interactions, eta-eta' and pi-pi', place domain VI in the core to position the lariat bond in the post-catalytic state. On the basis of structural and biochemical data, we propose that pi-pi' is a dynamic interaction that mediates the transition between the two steps of splicing, with eta-eta' serving an ancillary role. The structure also reveals a four-magnesium-ion cluster involved in both catalysis and positioning of the 5' end. Given the evolutionary relationship between group II and nuclear introns, it is likely that this active site configuration exists in the spliceosome as well.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4197185/" target="_blank"〉〈img src="https://static.pubmed.gov/portal/portal3rc.fcgi/4089621/img/3977009" border="0"〉〈/a〉 〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4197185/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Robart, Aaron R -- Chan, Russell T -- Peters, Jessica K -- Rajashankar, Kanagalaghatta R -- Toor, Navtej -- 5R01GM102216/GM/NIGMS NIH HHS/ -- 5T32GM007240/GM/NIGMS NIH HHS/ -- 5T32GM008326/GM/NIGMS NIH HHS/ -- 8P41GM103403-10/GM/NIGMS NIH HHS/ -- P41 GM103403/GM/NIGMS NIH HHS/ -- R01 GM102216/GM/NIGMS NIH HHS/ -- T32 GM007240/GM/NIGMS NIH HHS/ -- T32 GM008326/GM/NIGMS NIH HHS/ -- England -- Nature. 2014 Oct 9;514(7521):193-7. doi: 10.1038/nature13790. Epub 2014 Sep 24.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Chemistry and Biochemistry, University of California, San Diego, La Jolla, California 92093, USA. ; NE-CAT and Department of Chemistry and Chemical Biology, Cornell University, Argonne National Laboratory, Argonne, Illinois 60439, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/25252982" target="_blank"〉PubMed〈/a〉
Keywords:
Biocatalysis
;
Catalytic Domain
;
Crystallography, X-Ray
;
Evolution, Molecular
;
*Introns/genetics
;
Magnesium/metabolism/pharmacology
;
Models, Molecular
;
*Nucleic Acid Conformation/drug effects
;
*Phaeophyta/chemistry/genetics
;
RNA Splicing/genetics
;
Ribosome Subunits, Large/genetics
;
Spliceosomes/chemistry
Print ISSN:
0028-0836
Electronic ISSN:
1476-4687
Topics:
Biology
,
Chemistry and Pharmacology
,
Medicine
,
Natural Sciences in General
,
Physics
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