Publication Date:
2014-07-22
Description:
The eukaryotic RNA exosome processes and degrades RNA by directing substrates to the distributive or processive 3' to 5' exoribonuclease activities of Rrp6 or Rrp44, respectively. The non-catalytic nine-subunit exosome core (Exo9) features a prominent central channel. Although RNA can pass through the channel to engage Rrp44, it is not clear how RNA is directed to Rrp6 or whether Rrp6 uses the central channel. Here we report a 3.3 A crystal structure of a ten-subunit RNA exosome complex from Saccharomyces cerevisiae composed of the Exo9 core and Rrp6 bound to single-stranded poly(A) RNA. The Rrp6 catalytic domain rests on top of the Exo9 S1/KH ring above the central channel, the RNA 3' end is anchored in the Rrp6 active site, and the remaining RNA traverses the S1/KH ring in an opposite orientation to that observed in a structure of a Rrp44-containing exosome complex. Solution studies with human and yeast RNA exosome complexes suggest that the RNA path to Rrp6 is conserved and dependent on the integrity of the S1/KH ring. Although path selection to Rrp6 or Rrp44 is stochastic in vitro, the fate of a particular RNA may be determined in vivo by the manner in which cofactors present RNA to the RNA exosome.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4310248/" 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/PMC4310248/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Wasmuth, Elizabeth V -- Januszyk, Kurt -- Lima, Christopher D -- F31 GM097910/GM/NIGMS NIH HHS/ -- F31GM097910/GM/NIGMS NIH HHS/ -- P30 CA008748/CA/NCI NIH HHS/ -- P41 GM111244/GM/NIGMS NIH HHS/ -- P41GM103403/GM/NIGMS NIH HHS/ -- P41GM103473/GM/NIGMS NIH HHS/ -- R01 GM079196/GM/NIGMS NIH HHS/ -- R01GM079196/GM/NIGMS NIH HHS/ -- Howard Hughes Medical Institute/ -- England -- Nature. 2014 Jul 24;511(7510):435-9. doi: 10.1038/nature13406. Epub 2014 Jul 6.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉1] Structural Biology Program, Sloan-Kettering Institute, 1275 York Avenue, New York, New York 10065, USA [2] Louis V. Gerstner Jr. Graduate School of Biomedical Sciences, Sloan-Kettering Institute, Memorial Sloan-Kettering Cancer Center, 1275 York Avenue, New York, New York 10065, USA. ; Structural Biology Program, Sloan-Kettering Institute, 1275 York Avenue, New York, New York 10065, USA. ; 1] Structural Biology Program, Sloan-Kettering Institute, 1275 York Avenue, New York, New York 10065, USA [2] Howard Hughes Medical Institute, 1275 York Avenue, New York, New York 10065, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/25043052" target="_blank"〉PubMed〈/a〉
Keywords:
Catalytic Domain
;
Crystallography, X-Ray
;
Exoribonucleases/metabolism
;
Exosome Multienzyme Ribonuclease Complex/*chemistry/*metabolism
;
Humans
;
Models, Molecular
;
Poly A/chemistry/*metabolism
;
RNA, Messenger/*chemistry/*metabolism
;
Saccharomyces cerevisiae/*chemistry
;
Saccharomyces cerevisiae Proteins/*chemistry/*metabolism
Print ISSN:
0028-0836
Electronic ISSN:
1476-4687
Topics:
Biology
,
Chemistry and Pharmacology
,
Medicine
,
Natural Sciences in General
,
Physics
