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RNA helicase DDX21 coordinates transcription and ribosomal RNA processing.
Nature 2015; 518(7538):249-53Nat

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+Show Affiliations

Department of Chemical and Systems Biology, Stanford University School of Medicine, Stanford, California 94305, USA.Howard Hughes Medical Institute and Program in Epithelial Biology, Stanford University School of Medicine, Stanford, California 94305, USA.Howard Hughes Medical Institute and Program in Epithelial Biology, Stanford University School of Medicine, Stanford, California 94305, USA.Howard Hughes Medical Institute and Program in Epithelial Biology, Stanford University School of Medicine, Stanford, California 94305, USA.Howard Hughes Medical Institute and Program in Epithelial Biology, Stanford University School of Medicine, Stanford, California 94305, USA.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.

Pub Type(s)

Journal Article
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

25470060

Citation

Calo, Eliezer, et al. "RNA Helicase DDX21 Coordinates Transcription and Ribosomal RNA Processing." Nature, vol. 518, no. 7538, 2015, pp. 249-53.
Calo E, Flynn RA, Martin L, et al. RNA helicase DDX21 coordinates transcription and ribosomal RNA processing. Nature. 2015;518(7538):249-53.
Calo, E., Flynn, R. A., Martin, L., Spitale, R. C., Chang, H. Y., & Wysocka, J. (2015). RNA helicase DDX21 coordinates transcription and ribosomal RNA processing. Nature, 518(7538), pp. 249-53. doi:10.1038/nature13923.
Calo E, et al. RNA Helicase DDX21 Coordinates Transcription and Ribosomal RNA Processing. Nature. 2015 Feb 12;518(7538):249-53. PubMed PMID: 25470060.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - RNA helicase DDX21 coordinates transcription and ribosomal RNA processing. AU - Calo,Eliezer, AU - Flynn,Ryan A, AU - Martin,Lance, AU - Spitale,Robert C, AU - Chang,Howard Y, AU - Wysocka,Joanna, Y1 - 2014/11/24/ PY - 2014/04/04/received PY - 2014/10/06/accepted PY - 2014/12/4/entrez PY - 2014/12/4/pubmed PY - 2015/2/28/medline SP - 249 EP - 53 JF - Nature JO - Nature VL - 518 IS - 7538 N2 - 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. SN - 1476-4687 UR - https://www.unboundmedicine.com/medline/citation/25470060/RNA_helicase_DDX21_coordinates_transcription_and_ribosomal_RNA_processing_ L2 - https://doi.org/10.1038/nature13923 DB - PRIME DP - Unbound Medicine ER -