RC3H1 (Roquin1) and RC3H2 (Roquin2) interactome
Ontology highlight
ABSTRACT:
INSTRUMENT(S): LTQ
ORGANISM(S): Homo Sapiens (ncbitaxon:9606)
SUBMITTER: 
Laurence Florens
PROVIDER: MSV000082202 | MassIVE | Fri Mar 23 10:40:00 GMT 2018
SECONDARY ACCESSION(S): PXD009312
REPOSITORIES: MassIVE
Similar Datasets
Project description:The RNA-binding protein RC3H1 (also known as ROQUIN) promotes TNFalpha mRNA decay via a 3'UTR constitutive decay element (CDE). Here, we applied PAR-CLIP to human RC3H1 to identify about 3800 mRNA targets with more than 16000 binding sites. A large number of sites are distinct from the consensus CDE and revealed a structure-sequence motif with U-rich sequences embedded in hairpins. RC3H1 binds preferentially short-lived and DNA damage induced mRNAs, indicating a role of this RNA-binding protein in the posttranscriptional regulation of the DNA damage response. Intriguingly, RC3H1 affects expression of NF-kB pathway regulators such as IkBalpha and A20. RC3H1 uses roquin and Zn-finger domains to contact a binding site in the A20 3'UTR, demonstrating a not yet recognized mode of RC3H1 binding. Knockdown of RC3H1 resulted in increased A20 protein expression, thereby interfering with IkB kinase and NF-kB activities, demonstrating that RC3H1 can modulate the activity of the IKK/NF-kB pathway.
2015-07-20 | GSE47078 | GEO
Project description:The RNA-binding protein RC3H1 (also known as ROQUIN) promotes TNFalpha mRNA decay via a 3'UTR constitutive decay element (CDE). Here, we applied PAR-CLIP to human RC3H1 to identify about 3800 mRNA targets with more than 16000 binding sites. A large number of sites are distinct from the consensus CDE and revealed a structure-sequence motif with U-rich sequences embedded in hairpins. RC3H1 binds preferentially short-lived and DNA damage induced mRNAs, indicating a role of this RNA-binding protein in the posttranscriptional regulation of the DNA damage response. Intriguingly, RC3H1 affects expression of NF-kB pathway regulators such as IkBalpha and A20. RC3H1 uses roquin and Zn-finger domains to contact a binding site in the A20 3'UTR, demonstrating a not yet recognized mode of RC3H1 binding. Knockdown of RC3H1 resulted in increased A20 protein expression, thereby interfering with IkB kinase and NF-kB activities, demonstrating that RC3H1 can modulate the activity of the IKK/NF-kB pathway.
2015-07-20 | GSE68611 | GEO
Project description:Roquin2, and its paralog Roquin1, are key regulator of mRNA decay. Roquin proteins recognize mRNAs containing a 3’-UTR stem-loop motif, called constitutive decay element (CDE), through the ROQ domain. Upon target engagement, Roquin proteins recruit the CCR4-CAF1-NOT complex, mediating mRNA deadenylation and destabilization. To study the effect of Roquin2 stabilization, we sought out to identify the relevant Roquin2 mRNA targets in human DLBCL. To this purpose, we measured differential gene expression via RNA-seq analysis in U-2932 cells expressing Roquin2 or non-degradable Roquin2 upon BCR crosslinking.
2018-04-27 | GSE93675 | GEO
Project description:Regulation of gene expression at the post-transcriptional level plays an indispensable role during TGFbeta-induced EMT and metastasis. This regulation involves a transcript-selective translational regulatory pathway in which a ribonucleoprotein (mRNP) complex, consisting of heterogeneous nuclear ribonucleoprotein E1 (hnRNP E1) and eukaryotic elongation factor 1A1 (eEF1A1), binds to a 3M-bM-^@M-^Y-UTR regulatory BAT (TGFM-NM-2 activated translation) element and silences translation of Dab2 and ILEI mRNAs, two transcripts which are involved in mediating EMT. TGFbeta activates a kinase cascade terminating in the phosphorylation of hnRNP E1, by isoform-specific stimulation of protein kinase B/Akt2, inducing the release of the mRNP complex from the 3M-bM-^@M-^Y-UTR element, resulting in the reversal of translational silencing and increased expression of Dab2 and ILEI transcripts. We adopted a combinatorial approach involving polysome profiling and RIP-Chip analyses using hnRNP E1 and filtered the array data based on the regulatory mechanism of Dab2 and ILEI. This led to the identification and validation of a cohort of target mRNAs that follow the same pattern of regulation as Dab2 and ILEI. To identify potential target mRNA transcripts that are translationally regulated by hnRNP E1 in a TGF-beta-dependent manner, we adopted a combinatorial approach involving expression profiling analyses and RNA immunoprecipitation analysis (RIP-Chip). We performed a screen using: 1) total mRNA and 2) RNA isolated from monosomal (non-translating) versus polysomal (translating) fractions from TGF-beta-treated (24 h) and non-treated NMuMG cells and from the hnRNP E1 knockdown derivative (E1KD), that undergo constitutive EMT even in the absence of TGF-beta. In addition, we screened for transcripts that selectively interact with hnRNP E1 in NMuMG cells under unstimulated conditions and subsequently lose their temporal association following TGF-beta stimulation. The samples were individually hybridized to Affymetrix GeneChipM-BM-. Mouse Genome 430 2.0 arrays.
2012-08-30 | E-GEOD-40466 | biostudies-arrayexpress
Project description:Both p150 and p110 isoforms of ADAR1 convert adenosine to inosine in double-stranded RNA (dsRNA). The p150 isoform suppresses the dsRNA sensing mechanism that activates the interferon induction mediated by the MDA5-MAVS signaling. In contrast, the biological function of the p110 isoform localized in the nucleus remains largely unknown. Here we show that stress-activated phosphorylation of ADAR1p110 by MKK6/p38 MAP kinases promotes its binding to Exportin-5 and nuclear export to the cytoplasm. Once translocated to the cytoplasmic, ADAR1p110 suppresses apoptosis of stressed cells by protecting many anti-apoptotic gene transcripts that contain 3’UTR dsRNA structures such as those consisting of inverted Alu repeats. ADAR1p110 competitively inhibits binding of Staufen1 to the 3’UTR dsRNAs and antagonizes the Staufen1-mediated mRNA decay mechanism. Our studies revealed a new stress response mechanism regulated by MAP kinases, in which ADAR1p110 translocates to the cytoplasm and regulates a class of mRNAs required for survival of stressed cells.
2017-03-21 | GSE85455 | GEO
Project description:Regulation of gene expression at the post-transcriptional level plays an indispensable role during TGFbeta-induced EMT and metastasis. This regulation involves a transcript-selective translational regulatory pathway in which a ribonucleoprotein (mRNP) complex, consisting of heterogeneous nuclear ribonucleoprotein E1 (hnRNP E1) and eukaryotic elongation factor 1A1 (eEF1A1), binds to a 3’-UTR regulatory BAT (TGFβ activated translation) element and silences translation of Dab2 and ILEI mRNAs, two transcripts which are involved in mediating EMT. TGFbeta activates a kinase cascade terminating in the phosphorylation of hnRNP E1, by isoform-specific stimulation of protein kinase B/Akt2, inducing the release of the mRNP complex from the 3’-UTR element, resulting in the reversal of translational silencing and increased expression of Dab2 and ILEI transcripts. We adopted a combinatorial approach involving polysome profiling and RIP-Chip analyses using hnRNP E1 and filtered the array data based on the regulatory mechanism of Dab2 and ILEI. This led to the identification and validation of a cohort of target mRNAs that follow the same pattern of regulation as Dab2 and ILEI.
2012-08-30 | GSE40466 | GEO
Project description:Precise control of protein synthesis by engineering sequence elements in 5’ untranslated region (5’UTR) remains a fundamental challenge. To accelerate our understanding of cis-regulatory code embedded in 5’UTR, we devised massively parallel reporter assays from a synthetic mRNA library composed of over one million 5’UTR variants. A completely randomized 10-nucleotide sequence preceding an upstream open reading frame (uORF) and downstream GFP leads to a broad range of mRNA translatability and stability in mammalian cells. While efficient translation protects mRNA from degradation, uORF translation triggers mRNA decay in a UPF1-dependent manner. We also identified translational inhibitory elements in 5’UTR with G-quadruplex as a mark for mRNA decay in the P-body. Unexpectedly, an unstructured A-rich element in 5’UTR, while enabling cap-independent translation, destabilizes mRNAs in the absence of translation. Our results not only expose diverse sequence features of 5’UTR in controlling mRNA translatability, but also reveal ribosome-dependent and -independent mRNA surveillance pathways.
2020-06-01 | GSE145046 | GEO
Project description:Given that RHA regulates translation by binding a PCE located at the 5’ UTR of the target transcripts a genome-wide screen was performed to identify mRNAs that bind RHA in vivo. The results from four experiments with samples obtained in four independent RNA immunoprecipitations identified 375 transcripts that co-immunoprecipitate with FLAG RHA.
2010-08-19 | GSE23688 | GEO
Project description:Given that RHA regulates translation by binding a PCE located at the 5’ UTR of the target transcripts a genome-wide screen was performed to identify mRNAs that bind RHA in vivo. The results from duplicate experiments with samples obtained in two independent RNA immunoprecipitations identified 407 transcripts that co-immunoprecipitate with FLAG RHA. Keywords: gene expression array-based
2008-12-20 | GSE14056 | GEO
Project description:Upon muscle injury the high mobility group box 1 (HMGB1) protein is up-regulated and secreted to initiate reparative responses. Here we show that HMGB1 controls myogenesis both in vitro and in vivo, during development and after adult muscle injury. HMGB1 expression in muscle cells is regulated at the translational level: the miRNA miR-1192 inhibits HMGB1 translation and the RNA-binding protein HuR promotes it. HuR binds to a cis-element, HuRBS, located in the 3'UTR of the HMGB1 transcript, and at the same time miR-1192 is recruited to an adjacent seed element. The binding of HuR to the HuRBS prevents the recruitment of Argonaute 2 (Ago2), overriding miR-1192-mediated translation inhibition. Depleting HuR reduces myoblast fusion and silencing miR-1192 re-establishes the fusion potential of HuR-depleted cells. We propose that HuR promotes the commitment of myoblasts to myogenesis by enhancing the translation of HMGB1 and suppressing the translation inhibition mediated by miR-1192. RNA content was extracted following immunoprecipitation of HuR using a monoclonal antibody (3A2) and the levels of mRNA were compared to an IgG control in order to determine which transcripts were enriched in the HuR ribonucleoprotein complex.
2013-08-14 | E-GEOD-49855 | biostudies-arrayexpress