RNA helicase DDX21 coordinates transcription and ribosomal RNA processing

DEAD-box RNA helicase DDX21 is involved in both the transcription and RNA processing of ribosomal genes in human cells, sensing the transcriptional status of both RNA polymerase I and RNA polymerase II and associating with non-coding RNAs involved in ribonucleoprotein formation, possibly allowing for coordinated regulation of protein synthesis. Role of DDX21 in ribosome biogenesis RNA helicases remodel RNA secondary structure and ribonucleoprotein (RNP) complexes during various steps of RNA metabolism. Here, Joanna Wysocka and colleagues find that a DEAD-box RNA helicase, DDX21, is involved in both the transcription and RNA processing of ribosomal genes in human cells. DDX21 senses the transcriptional status of RNA polymerases I and II, and associates with non-coding RNAs involved in RNP formation. These broad interactions in different nuclear compartments are specific for ribosomal biogenesis and may allow coordinated regulation of protein synthesis. DEAD-box RNA helicases are vital for the regulation of various aspects of the RNA life cycle 1 , 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 bi