Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P50583 (asymmetrical)
 12,197 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

A number of eukaryotic proteins are already known to orchestrate key steps of mRNA metabolism and translation via interactions with the 5' m7GpppN cap. We have characterized a new type of histidine triad (HIT) motif protein (Nhm1) that co-purifies with the cap-binding complex eIF4F of Schizosaccharomyces pombe. Nhm1 is an RNA-binding protein that binds to m7GTP-Sepharose, albeit with lower specificity and affinity for methylated GTP than is typical for the cap-binding protein known as eukaryotic initiation factor 4E. Sequence searches have revealed that proteins with strong sequence similarity over all regions of the new protein exist in a wide range of eukaryotes, yet none has been characterized up to now. However, other proteins that share specific motifs with Nhm1 include the human Fhit tumour suppressor protein and the diadenosine 5', 5"'-P1, P4-tetraphosphate asymmetrical hydrolase of S. pombe. Our experimental work also reveals that Nhm1 inhibits translation in a cell-free extract prepared from S. pombe, and that it is therefore a putative translational modulator. On the other hand, purified Nhm1 manifests mRNA decapping activity, yet is physically distinct from the Saccharomyces cerevisiae decapping enzyme Dcp1. Moreover, fluorescence and immunofluorescence microscopy show that Nhm1 is predominantly, although not exclusively, nuclear. We conclude that Nhm1 has evolved as a special branch of the HIT motif superfamily that has the potential to influence both the metabolism and the translation of mRNA, and that its presence in S. pombe suggests the utilization of a novel decapping pathway.
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PMID:A nuclear protein in Schizosaccharomyces pombe with homology to the human tumour suppressor Fhit has decapping activity. 1236 30

Musashi has been identified as an RNA-binding protein thought to be involved in asymmetric divisions during Drosophila neural development. To analyze expression patterns of mammalian Musashi homolog Musashi-1 in human normal colon crypt, 155 colon crypts separated from biopsy specimens of normal colonic mucosa were evaluated. Specimens were fixed, microdissected to isolate a few crypts, immunostained with anti-Musashi-1 antibody (14H1), and examined under confocal laser scan microscopy. The number of Musashi-1-positive cells in each crypt was 19.0 +/- 7.53 (mean +/- SD). Most Musashi-1 positive cells were located at the crypt base, between cell positions 1 and 10. Distribution of Musashi-1-positive cells corresponded with that of stem cells, as outlined in previous reports, implying that Musashi-1 is a key control element of asymmetrical division within the colon crypt. This is the first report outlining expression of Musashi-1 in human colon crypt cells.
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PMID:Expression of Musashi-1 in human normal colon crypt cells: a possible stem cell marker of human colon epithelium. 1292 47

The pathogenicity determinants of Citrus tristeza virus (CTV) are presently unknown, although transgenic Mexican limes over-expressing CTV p23, an RNA-binding protein involved in regulating the asymmetrical accumulation of viral RNA strands, display typical CTV symptoms. Here we compared the predominant sequence variants of gene p23 from 18 CTV isolates of different geographic origin and pathogenicity characteristics. Phylogenetic analysis of these sequences revealed three groups of isolates: i) mild, inducing only symptoms in lime and/or decline of citrus species grafted on sour orange rootstock, ii) severe, causing additionally stem pitting on sweet orange and/or grapefruit, and iii) an atypical group of isolates inciting variable symptoms. The sequences of the isolates located at the periphery of each group were recombinants. Pairwise comparisons of the predicted amino acid sequences showed that residues at positions 78-80 were characteristic of each group of isolates. Group-specific primers based on these differences allowed RT-PCR detection of each sequence type in dsRNA-rich preparations from infected tissues. While mild isolates contained only the sequence characteristic of this group, most severe isolates contained the sequences characteristic of their group, and additionally, sequences characteristic of the mild and/or the atypical groups, suggesting that the severe phenotype is associated with the presence of the severe and/or the atypical sequence types. This association can be exploited for quick detection of potentially damaging sequence variants and for monitoring cross protection.
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PMID:Polymorphism of a specific region in gene p23 of Citrus tristeza virus allows discrimination between mild and severe isolates. 1464 89

The large RNA genome of Citrus tristeza virus (CTV; ca. 20 kb) contains 12 open reading frames, with the 3'-terminal one corresponding to a protein of 209 amino acids (p23) that is expressed from an abundant subgenomic RNA. p23, an RNA-binding protein with a putative zinc-finger domain and some basic motifs, is unique to CTV because no homologs have been found in other closteroviruses, including the type species of the genus Beet yellows virus (despite both viruses having many homologous genes). Consequently, p23 might have evolved for the specific interaction of CTV with its citrus hosts. From a functional perspective p23 has been involved in many roles: (i) regulation of the asymmetrical accumulation of CTV RNA strands, (ii) induction of the seedling yellows syndrome in sour orange and grapefruit, (iii) intracellular suppression of RNA silencing, (iv) elicitation of CTV-like symptoms when expressed ectopically as a transgene in several Citrus spp., and (v) enhancement of systemic infection (and virus accumulation) in sour orange and CTV release from the phloem in p23-expressing transgenic sweet and sour orange. Moreover, transformation of Mexican lime with intron-hairpin constructs designed for the co-inactivation of p23 and the two other CTV silencing suppressors results in complete resistance against the homologous virus. From a cellular point of view, recent data indicate that p23 accumulates preferentially in the nucleolus, being the first closterovirus protein with such a subcellular localization, as well as in plasmodesmata. These major accumulation sites most likely determine some of the functional roles of p23.
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PMID:Citrus tristeza virus p23: a unique protein mediating key virus-host interactions. 2365 24