A Tetrahymena Hsp90 co‐chaperone promotes siRNA loading by ATP‐dependent and ATP‐independent mechanisms. (14th January 2015)

• Record Type: Journal Article
• Authors: Woehrer, Sophie L; Aronica, Lucia; Suhren, Jan H; Busch, Clara Jana‐Lui; Noto, Tomoko; Mochizuki, Kazufumi
• Is Part Of: EMBO journal. Volume 34:Number 4(2015)
• Page Start: 559
• Page End: 577
• Publication Date: 2015-01-14
• Subjects: Molecular biology -- Periodicals; 572.805
• DOI: 10.15252/embj.201490062
• Languages: English
• ISSNs: 0261-4189

Abstract

<abstract abstract-type="main" id="embj201490062-abs-0001"> <title>Abstract</title> <p>The loading of small interfering RNAs (siRNAs) and microRNAs into Argonaute proteins is enhanced by Hsp90 and ATP in diverse eukaryotes. However, whether this loading also occurs independently of Hsp90 and ATP remains unclear. We show that the <italic>Tetrahymena</italic> Hsp90 co‐chaperone Coi12p promotes siRNA loading into the Argonaute protein Twi1p in both ATP‐dependent and ATP‐independent manners <italic>in vitro</italic>. The ATP‐dependent activity requires Hsp90 and the tetratricopeptide repeat (TPR) domain of Coi12p, whereas these factors are dispensable for the ATP‐independent activity. Both activities facilitate siRNA loading by counteracting the Twi1p‐binding protein Giw1p, which is important to specifically sort the 26‐ to 32‐nt siRNAs to Twi1p. Although Coi12p lacking its TPR domain does not bind to Hsp90, it can partially restore the siRNA loading and DNA elimination defects of <italic>COI12</italic> knockout cells, suggesting that Hsp90‐ and ATP‐independent loading of siRNA occurs <italic>in vivo</italic> and plays a physiological role in <italic>Tetrahymena</italic>.</p> </abstract>