Letter | Published:

RNA helicase DDX21 coordinates transcription and ribosomal RNA processing

Nature volume 518, pages 249253 (12 February 2015) | Download Citation


DEAD-box RNA helicases are vital for the regulation of various aspects of the RNA life cycle1, 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.

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Gene Expression Omnibus

Data deposits

All sequencing data have been deposited in Gene Expression Omnibus (GEO) data repository under accession number GSE56802.


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We thank D. H. Price for the LARP7 antibody, K. Lane from M. Covert’s laboratory for metabolic inhibitors, K. Cimprich and members of the Chang and Wysocka laboratories for discussions, and B. Zarnegar and P. Khavari for discussions regarding iCLIP. This work was supported by the Stanford Medical Scientist Training Program and T32CA09302 (R.A.F.), AP Giannini Foundation (R.C.S.), National Institutes of Health grants R01-HG004361, R01-ES023168, P50-HG007735 (H.Y.C.) and R01-GM095555 (J.W.), W. M. Keck Foundation (J.W.), and Helen Hay Whitney Foundation (E.C.). H.Y.C. is an Early Career Scientist of the Howard Hughes Medical Institute.

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Author notes

    • Eliezer Calo
    •  & Ryan A. Flynn

    These authors contributed equally to this work.


  1. Department of Chemical and Systems Biology, Stanford University School of Medicine, Stanford, California 94305, USA

    • Eliezer Calo
    •  & Joanna Wysocka
  2. Howard Hughes Medical Institute and Program in Epithelial Biology, Stanford University School of Medicine, Stanford, California 94305, USA

    • Ryan A. Flynn
    • , Lance Martin
    • , Robert C. Spitale
    •  & Howard Y. Chang
  3. Department of Developmental Biology, Stanford University School of Medicine, Stanford, California 94305, USA

    • Joanna Wysocka


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H.Y.C. and J.W. supervised the project; E.C. and R.A.F. conceived and designed the study; E.C. and R.A.F. performed experiments and analysed ChIP-seq data. R.A.F. performed iCLIP and L.M., R.C.S. and R.A.F. analysed iCLIP data; R.A.F., E.C., J.W. and H.Y.C. wrote the manuscript with input from all co-authors.

Competing interests

The authors declare no competing financial interests.

Corresponding authors

Correspondence to Howard Y. Chang or Joanna Wysocka.

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    Supplementary Table I

    This fie contains oligonucleotides utilized in this study.

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