CNBP is a eukaryote-conserved nucleic-acid binding protein required in mammals for embryonic development. It contains seven CCHC-type zinc-finger domains and was suggested to act as a nucleic acid chaperone, as well as a transcription factor. Here, we identify all CNBP isoforms as cytoplasmic messenger RNA (mRNA)-binding proteins. Using Photoactivatable Ribonucleoside Enhanced Cross-linking and Immunoprecipitation, we mapped its binding sites on RNA at nucleotide-level resolution on a genome-wide scale and find that CNBP interacted with 3961 mRNAs in human cell lines, preferentially at a G-rich motif close to the AUG start codon on mature mRNAs. Loss- and gain-of-function analyses coupled with system-wide RNA and protein quantification revealed that CNBP did not affect RNA abundance, but rather promoted translation of its targets. This is consistent with an RNA chaperone function of CNBP helping to resolve secondary structures, thus promoting translation. Overall design: CNBP protein knockdown and RNA-seq
The Human CCHC-type Zinc Finger Nucleic Acid-Binding Protein Binds G-Rich Elements in Target mRNA Coding Sequences and Promotes Translation.
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View SamplesCellular drug resistance is associated with an unfavorable prognosis in pediatric acute lymphoblastic leukemia (ALL). To identify genes conferring resistance to antileukemic agents, we analyzed the expression of >12,700 genes in sensitive and resistant ALL cells obtained at diagnosis from 174 patients. This revealed 42, 59, 54 and 22 genes (P0.001) that were differentially expressed in B-lineage ALL that was sensitive versus resistant to prednisolone, vincristine, asparaginase or daunorubicin, respectively, with prediction accuracies of 71-76%. Notably, 149 of the discriminating genes have not been previously associated with resistance to these anticancer agents. These included carbohydrate-metabolism and transcription-associated genes for prednisolone, cytoskeleton and extracellular matrix genes for vincristine, ribosomal protein and translation-associated genes for asparaginase, and RAS signaling and nucleosome remodeling complex genes for daunorubicin. The identification of novel genomic determinants of cellular drug resistance provides new insights for overcoming drug resistance in acute lymphoblastic leukemia.
Gene-expression patterns in drug-resistant acute lymphoblastic leukemia cells and response to treatment.
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View Samplesprimary ALL cells (B- and T-lineage) sensitive to daunorubicinby the MTT in vitro sensitivity assay
Gene-expression patterns in drug-resistant acute lymphoblastic leukemia cells and response to treatment.
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View Samplesprimary ALL cells (B- and T-lineage) sensitive to vincristine by the MTT in vitro sensitivity assay
Gene-expression patterns in drug-resistant acute lymphoblastic leukemia cells and response to treatment.
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View Samplesprimary ALL cells (B-lineage) sensitive to daunorubicin by the MTT in vitro sensitivity assay
Gene-expression patterns in drug-resistant acute lymphoblastic leukemia cells and response to treatment.
No sample metadata fields
View Samplesprimary ALL cells (B- and T-lineage) sensitive to L-asparaginase by the MTT in vitro sensitivity assay
Gene-expression patterns in drug-resistant acute lymphoblastic leukemia cells and response to treatment.
No sample metadata fields
View Samplesprimary ALL cells (B-lineage) sensitive to vincristine by the MTT in vitro sensitivity assay
Gene-expression patterns in drug-resistant acute lymphoblastic leukemia cells and response to treatment.
No sample metadata fields
View Samplesprimary ALL cells (B-lineage) sensitive to L-asparaginase by the MTT in vitro sensitivity assay
Gene-expression patterns in drug-resistant acute lymphoblastic leukemia cells and response to treatment.
No sample metadata fields
View Samplesprimary ALL cells (B- and T-lineage) sensitive to prednisolone by the MTT in vitro sensitivity assay
Gene-expression patterns in drug-resistant acute lymphoblastic leukemia cells and response to treatment.
No sample metadata fields
View Samplesprimary ALL cells (B- and T-lineage) resistant to L-asparaginase by the MTT in vitro sensitivity assay
Gene-expression patterns in drug-resistant acute lymphoblastic leukemia cells and response to treatment.
No sample metadata fields
View Samples