title: RNA helicase DDX21 coordinates transcription and ribosomal RNA processing.
abstract: DEAD-box RNA helicases are vital for the regulation of various aspects of the RNA life cycle, but the molecular underpinnings of their involvement, particularly in mammalian cells, remain poorly understood. Here we show that the DEAD-box RNA helicase DDX21 can sense the transcriptional status of both RNA polymerase (Pol) I and II to control multiple steps of ribosome biogenesis in human cells. We demonstrate that DDX21 widely associates with Pol I- and Pol II-transcribed genes and with diverse species of RNA, most prominently with non-coding RNAs involved in the formation of ribonucleoprotein complexes, including ribosomal RNA, small nucleolar RNAs (snoRNAs) and 7SK RNA. Although broad, these molecular interactions, both at the chromatin and RNA level, exhibit remarkable specificity for the regulation of ribosomal genes. In the nucleolus, DDX21 occupies the transcribed rDNA locus, directly contacts both rRNA and snoRNAs, and promotes rRNA transcription, processing and modification. In the nucleoplasm, DDX21 binds 7SK RNA and, as a component of the 7SK small nuclear ribonucleoprotein (snRNP) complex, is recruited to the promoters of Pol II-transcribed genes encoding ribosomal proteins and snoRNAs. Promoter-bound DDX21 facilitates the release of the positive transcription elongation factor b (P-TEFb) from the 7SK snRNP in a manner that is dependent on its helicase activity, thereby promoting transcription of its target genes. Our results uncover the multifaceted role of DDX21 in multiple steps of ribosome biogenesis, and provide evidence implicating a mammalian RNA helicase in RNA modification and Pol II elongation control.
authors.affiliation: Department of Chemical and Systems Biology, Stanford University School of Medicine, Stanford, California 94305, USA.
authors.forename: Eliezer
authors.initials: E
authors.lastname: Calo
authors.affiliation: Howard Hughes Medical Institute and Program in Epithelial Biology, Stanford University School of Medicine, Stanford, California 94305, USA.
authors.forename: Ryan A
authors.initials: RA
authors.lastname: Flynn
authors.affiliation: Howard Hughes Medical Institute and Program in Epithelial Biology, Stanford University School of Medicine, Stanford, California 94305, USA.
authors.forename: Lance
authors.initials: L
authors.lastname: Martin
authors.affiliation: Howard Hughes Medical Institute and Program in Epithelial Biology, Stanford University School of Medicine, Stanford, California 94305, USA.
authors.forename: Robert C
authors.initials: RC
authors.lastname: Spitale
authors.affiliation: Howard Hughes Medical Institute and Program in Epithelial Biology, Stanford University School of Medicine, Stanford, California 94305, USA.
authors.forename: Howard Y
authors.initials: HY
authors.lastname: Chang
authors.affiliation: 1] Department of Chemical and Systems Biology, Stanford University School of Medicine, Stanford, California 94305, USA [2] Department of Developmental Biology, Stanford University School of Medicine, Stanford, California 94305, USA.
authors.forename: Joanna
authors.initials: J
authors.lastname: Wysocka
mesh_terms: D002843:Chromatin / Q000235:genetics / Q000378:metabolism; D053487:DEAD-box RNA Helicases / Q000378:metabolism*; D020459:Genes, rRNA / Q000235:genetics*; D006801:Humans; D042925:Positive Transcriptional Elongation Factor B / Q000378:metabolism; D011485:Protein Binding; D012318:RNA Polymerase I / Q000378:metabolism; D012319:RNA Polymerase II / Q000378:metabolism; D012323:RNA Processing, Post-Transcriptional; D012335:RNA, Ribosomal / Q000096:biosynthesis* / Q000235:genetics / Q000378:metabolism*; D020537:RNA, Small Nucleolar / Q000235:genetics / Q000378:metabolism; D016601:RNA-Binding Proteins / Q000378:metabolism; D017411:Ribonucleoproteins, Small Nuclear / Q000737:chemistry / Q000378:metabolism; D014158:Transcription, Genetic
chemical_list: D002843:Chromatin; D012335:RNA, Ribosomal; D020537:RNA, Small Nucleolar; D016601:RNA-Binding Proteins; D017411:Ribonucleoproteins, Small Nuclear; D042925:Positive Transcriptional Elongation Factor B; D012319:RNA Polymerase II; D012318:RNA Polymerase I; C501726:DDX21 protein, human; D053487:DEAD-box RNA Helicases