title: Alternate rRNA secondary structures as regulators of translation.
abstract: Structural dynamics of large molecular assemblies are intricately linked to function. For ribosomes, macromolecular changes occur especially during mRNA translation and involve participation of ribosomal RNA. Without suitable probes specific to RNA secondary structure, however, elucidation of more subtle dynamic ribosome structure-function relationships, especially in vivo, remains challenging. Here we report that the Z-DNA- and Z-RNA-binding domain Zα, derived from the human RNA editing enzyme ADAR1-L, binds with high stability to specific rRNA segments of Escherichia coli and human ribosomes. Zα impaired in Z-RNA recognition does not associate with ribosomes. Notably, Zα(ADAR1)-ribosome interaction blocks translation in vitro and in vivo, with substantial physiological consequences. Our study shows that ribosomes can be targeted by a protein that specifically recognizes an alternate rRNA secondary structure, and suggests a new mechanism of translational regulation on the ribosome.
authors.affiliation: Division of Genomics and Genetics, School of Biological Sciences, Nanyang Technological University, Singapore, Singapore.
authors.forename: Shu
authors.initials: S
authors.lastname: Feng
authors.forename: Heng
authors.initials: H
authors.lastname: Li
authors.forename: Jing
authors.initials: J
authors.lastname: Zhao
authors.forename: Konstantin
authors.initials: K
authors.lastname: Pervushin
authors.forename: Ky
authors.initials: K
authors.lastname: Lowenhaupt
authors.forename: Thomas U
authors.initials: TU
authors.lastname: Schwartz
authors.forename: Peter
authors.initials: P
authors.lastname: Dröge
mesh_terms: D000243:Adenosine Deaminase / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism*; D002460:Cell Line; D043542:DNA, Z-Form / Q000378:metabolism; D004926:Escherichia coli / Q000378:metabolism; D006801:Humans; D008958:Models, Molecular; D009154:Mutation; D009690:Nucleic Acid Conformation; D011485:Protein Binding; D014176:Protein Biosynthesis; D017434:Protein Structure, Tertiary; D017393:RNA Editing; D012329:RNA, Bacterial / Q000737:chemistry / Q000378:metabolism; D012335:RNA, Ribosomal / Q000737:chemistry* / Q000378:metabolism*; D016601:RNA-Binding Proteins; D012270:Ribosomes / Q000378:metabolism
chemical_list: D043542:DNA, Z-Form; D012329:RNA, Bacterial; D012335:RNA, Ribosomal; D016601:RNA-Binding Proteins; C567955:ADARB1 protein, human; D000243:Adenosine Deaminase