Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0001486 (Adenovirus)
 3,125 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The reported binding preference of human hnRNP protein A1 for the 3'-splice site of some introns (Swanson and Dreyfuss (1988) EMBO J. 7, 3519-3529; Mayrand and Pederson (1990) Nucleic Acids Res. 18, 3307-3318) was tested by assaying in vitro the binding of purified recombinant A1 protein (expressed in bacteria) to synthetic oligodeoxynucleotides (21-mers) of suitable sequence. In such a minimal system we find preferential binding of protein A1 to oligodeoxynucleotide sequences corresponding to the 3'-splice site of IVS1 of human beta-globin pre-mRNA and of IVS1 of Adenovirus type 2 major late transcript. Mutation studies demonstrate that the binding specificity is dependent on the known critical domains of this intron region, the AG splice site dinucleotide and polypyrimidine tract, and resides entirely in the short oligonucleotide sequence. Moreover specific binding does not require the presence of other hnRNP proteins or of snRNP particles. Studies with a truncated recombinant protein demonstrated that the minimal protein sequence determinants for A1 recognition of 3'-splice acceptor site reside entirely in the N-terminal 195 aa of the unmodified protein.
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PMID:Recombinant hnRNP protein A1 and its N-terminal domain show preferential affinity for oligodeoxynucleotides homologous to intron/exon acceptor sites. 225 Nov 20

Viruses promote infection by hijacking the ubiquitin machinery of the host to counteract or redirect cellular processes. Adenovirus encodes two early proteins, E1B55K and E4orf6, that together co-opt a cellular ubiquitin ligase complex to overcome host defences and promote virus production. Adenovirus mutants lacking E1B55K or E4orf6 display defects in viral RNA processing and protein production, but previously identified substrates of the redirected ligase do not explain these phenotypes. Here, we used a quantitative proteomics approach to identify substrates of E1B55K/E4orf6-mediated ubiquitination that facilitate RNA processing. While all currently known cellular substrates of E1B55K and E4orf6 are degraded by the proteasome, we uncovered RNA-binding proteins as high-confidence substrates that are not decreased in overall abundance. We focused on two RNA-binding proteins, RALY and hnRNP-C, which we confirm are ubiquitinated without degradation. Knockdown of RALY and hnRNP-C increased levels of viral RNA splicing, protein abundance and progeny production during infection with E1B55K-deleted virus. Furthermore, infection with E1B55K-deleted virus resulted in an increased interaction of hnRNP-C with viral RNA and attenuation of viral RNA processing. These data suggest that viral-mediated ubiquitination of RALY and hnRNP-C relieves a restriction on viral RNA processing and reveal an unexpected role for non-degradative ubiquitination in the manipulation of cellular processes during virus infection.
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PMID:Adenovirus-mediated ubiquitination alters protein-RNA binding and aids viral RNA processing. 3266 14