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Genome-wide profiling of RNA Polymerase II, MITF and DDX21 occupancy in human A375 cells stably expressing either empty vector or HA-tagged PRL3.

ABSTRACT: To determine the role of PRL3 in gene regulation, empty vector or HA-tagged PRL3 was stably expressed in cultured human melanoma A375 cells. ChIP-seq was used to determine the impact of increased PRL3 expression on the genome-wide distribution of RNA Polymerase II (Total/Ser5-Phosphorylated/Ser2-Phosphorylated), MITF and DDX21. In combination with transcriptional analysis (4sU-seq; GEO accession - GSE127855), this study demonstrated that PRL3 overexpression leads to reduced RNA polymerase processivity at a subset of so called 'restricted' genes which are enriched for endolysosomal functions.

ORGANISM(S): Homo sapiens

PROVIDER: GSE149929 | GEO | 2020/07/20

REPOSITORIES: GEO

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RNA helicase DDX21 coordinates transcription and noncoding RNA processing of the ribosomal pathway

Project description: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 transcriptional status of both RNA Pol I and Pol II to control transcriptional and post-transcriptional 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 protein-coding and noncoding RNAs. Although broad, these molecular interactions, both at the chromatin and at the RNA level, exhibit a remarkable specificity for the ribosomal pathway. In the nucleolus, DDX21 occupies the transcribed rDNA locus, directly contacts both rRNA and snoRNAs and, as a functional component of the snoRNA ribonucleoprotein (snoRNP) complex, promotes modification of rRNA. In the nucleoplasm, DDX21 is incorporated into the 7SK snRNP complex, which facilitates DDX21 association with promoters of Pol II-transcribed genes encoding ribosomal proteins and snoRNAs. Promoter-bound DDX21 facilitates the release of P-TEFb from the 7SK snRNP, enhancing productive Pol II elongation. Altogether, we present a unifying mechanism for the coordinated regulation of ribosomal genes across nuclear compartments, and provide first evidence implicating a mammalian RNA helicase in RNA modification and Pol II elongation control. Examination of DDX21 chromatin association and DDX21 RNA interacting partners in HEK293 cells

2014-11-17 | E-GEOD-56802 | biostudies-arrayexpress

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2023-01-05 | PXD028561 | Pride

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Project description:The RNA helicase DDX21 acts as trancriptional sensor for nucleotide lowering

2020-02-04 | GSE128085 | GEO

Identification of Amino Enhancer of Split (AES) and DDX21 binding snoRNAs by RIP-Seq.

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Glucose dissociates DDX21 dimers to regulate mRNA processing and promote epidermal differentiation (CUT&RUN)

Project description:Glucose is an important cellular energy source, however, glucose’s function as a second messenger remains relatively unexplored. Here, we find that glucose binds directly to DDX21 to regulate its function during epidermal differentiation. Specifically, glucose binds to the ATP-binding domain of DDX21 to induce a conformational change and inhibit helicase activity. Glucose binding inhibits the dimerization of DDX21 leading to re-localization from the nucleolus to the nucleoplasm and reassembly of DDX21 into larger protein complexes, increasing its association with splicing factors. This occurs during keratinocyte differentiation, where glucose accumulation is necessary, and results in DDX21 binding to RNA processing proteins and mRNA introns. Consequently, DDX21 regulates the splicing of key differentiation factors and promotes epidermal differentiation in a glucose-dependent manner. These findings reveal a novel mechanism of glucose regulation of cell signaling.

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