11/7/2023 0 Comments Input in iclipE., Saiakhova, A., Manaenkov, P., Adams, M. The DEXD/H-box RNA helicase RHII/Gu is a co-factor for c-Jun-activated transcription. Down-regulation of RNA helicase II/Gu results in the depletion of 18 and 28 S rRNAs in Xenopus oocyte. Silencing of RNA helicase II/Guα inhibits mammalian ribosomal RNA production. DEAD-box helicases as integrators of RNA, nucleotide and protein binding. Toward a molecular understanding of RNA remodeling by DEAD-box proteins. DEAD-box proteins: the driving forces behind RNA metabolism. 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. 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. 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. In the nucleolus, DDX21 occupies the transcribed rDNA locus, directly contacts both rRNA and snoRNAs, and promotes rRNA transcription, processing and modification. Although broad, these molecular interactions, both at the chromatin and RNA level, exhibit remarkable specificity for the regulation of ribosomal genes. 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. 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. 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.
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