Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: EC:3.1.1.53 (sialidase)
 2,694 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

We have totally sequenced a cytosolic sialidase [EC 3.2.1.18] by RT-PCR from the murine thymus (murine thymic sialidase, MTS) which has a 1844-base length (encoding 385 amino acids including two sialidase motifs) and is the longest cytosolic sialidase ever reported. MTS has high and relatively low homologies with those of mammalian cytosolic sialidases from the mouse brain (99%), rat (91%), and human skeletal muscle (75%), and those of the mouse lysosomal (47%) and membrane-bound (51%) sialidases, respectively. Chromosomal mapping, being the first report of mouse cytosolic sialidase gene, showed that the MTS gene is localized to the distal part of mouse chromosome 1D and to rat chromosome 9q36. RT-PCR with the site-specific primers revealed that the coding region was expressed in all organs tested, but expressions including the 5'-UTR were barely detectable except for in the upper-thymic fraction. Also, soluble sialidase activity in the thymus was the highest of these organs. There were mRNA instability signals and AT-rich regions in 143 bp of MTS 5'-end.
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PMID:Cloning, chromosomal mapping, and characteristic 5'-UTR sequence of murine cytosolic sialidase. 1150 29

The deficiency of the lysosomal neuraminidase (NEU1; sialidase) causes the storage disorder sialidosis with symptoms ranging from eye abnormalities and neurological disturbances to skeletal malformations, mental retardation and early death. Sialidosis patients encompassing a wide spectrum of clinical symptoms were screened for mutations in neu1. We identified the same homozygous interstitial deletion (11 kb) in two patients causing the fusion of exon 10 of CTL4 (New Gene 22; NG22) with the 3'-UTR of neu1. In one patient we found the resulting CTL4/Neu1 fusion transcript, in the other we detected an alternatively spliced CTL4 transcript (retention of intron 9).
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PMID:Identification of a CTL4/Neu1 fusion transcript in a sialidosis patient. 1206 18

In trypanosomatids, transcription is polycistronic and gene expression control occurs mainly at the post-transcriptional level. To investigate the role of sequences present in the 3'UTR of stage-specific mRNAs of Trypanosoma cruzi, we generated a new vector, named pTcDUALuc, containing the firefly and Renilla luciferase reporter genes. To test this vector, sequences derived from the 3'UTR plus intergenic regions of the alpha tubulin gene, which is up-regulated in epimastigotes, and amastin, which is up-regulated in amastigotes, were inserted downstream from the firefly reporter gene and luciferase activity was compared in transient and stable transfected parasites. As expected, increased luciferase activity was detected in epimastigotes transiently transfected with pTcDUALuc containing tubulin sequences. Using stable transfected cell lines that were allowed to differentiate into amastigotes, we observed increased luciferase activity and mRNA levels in amastigotes transfected with pTcDUALuc containing amastin sequences. We also showed that the spliced leader sequence and poly-A tail were inserted in the predicted sites of the firefly luciferase mRNA and that deletions in the alpha tubulin 3'UTR resulted in decreased luciferase expression because it affects polyadenylation. In contrast to the constructs containing 3'UTR sequences derived from tubulin and amastin genes, the presence of the 3'UTR from a trans-sialidase gene, whose expression is higher in trypomastigotes, resulted in increased luciferase activity in trypomastigotes without a corresponding increase in luciferase mRNA levels.
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PMID:Development of a dual reporter system to identify regulatory cis-acting elements in untranslated regions of Trypanosoma cruzi mRNAs. 2127 85

T. cruzi improves the likelihood of invading or adapting to the host through its capacity to present a large repertoire of surface molecules. The metacyclic stage-specific surface glycoprotein GP82 has been implicated in host cell invasion. GP82 is encoded by multiple genes from the trans-sialidase superfamily. GP82 shows a modular organization, with some variation of N-terminal region flanking a conserved central core where the binding sites to the mammalian cell and gastric mucin are located. The function of GP82 as adhesin in host cell invasion process could expose the protein to an intense conservative and selective pressure. GP82 is a GPI-anchored surface protein, synthesized as a 70 kDa precursor devoid of N-linked sugars. GPI-minus variants accumulate in the ER indicating that GPI anchor acts as a forward transport signal for progressing along the secretory pathway as suggested for T. cruzi mucins. It has been demonstrated that the expression of GP82 is constitutive and may be regulated at post-transcriptional level, for instance, at translational level and/or mRNA stabilization. GP82 mRNAs are mobilized to polysomes and consequently translated, but only in metacyclic trypomastigotes. Analysis of transgenic parasites indicates that the mechanism regulating GP82 expression involves multiple elements in the 3'UTR.
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PMID:Genetic structure and expression of the surface glycoprotein GP82, the main adhesin of Trypanosoma cruzi metacyclic trypomastigotes. 2343 Dec 51

Trypanosomes, protozoan parasites of medical importance, essentially rely on post-transcriptional mechanisms to regulate gene expression in insect vectors and vertebrate hosts. RNA binding proteins (RBPs) that associate to the 3'-UTR of mature mRNAs are thought to orchestrate master developmental programs for these processes to happen. Yet, the molecular mechanisms by which differentiation occurs remain largely unexplored in these human pathogens. Here, we show that ectopic inducible expression of the RBP TcUBP1 promotes the beginning of the differentiation process from non-infective epimastigotes to infective metacyclic trypomastigotes in Trypanosoma cruzi. In early-log epimastigotes TcUBP1 promoted a drop-like phenotype, which is characterized by the presence of metacyclogenesis hallmarks, namely repositioning of the kinetoplast, the expression of an infective-stage virulence factor such as trans-sialidase, increased resistance to lysis by human complement and growth arrest. Furthermore, TcUBP1-ectopic expression in non-infective late-log epimastigotes promoted full development into metacyclic trypomastigotes. TcUBP1-derived metacyclic trypomastigotes were infective in cultured cells, and developed normally into amastigotes in the cytoplasm. By artificial in vivo tethering of TcUBP1 to the 3' untranslated region of a reporter mRNA we were able to determine that translation of the reporter was reduced by 8-fold, while its mRNA abundance was not significantly compromised. Inducible ectopic expression of TcUBP1 confirmed its role as a translational repressor, revealing significant reduction in the translation rate of multiple proteins, a reduction of polysomes, and promoting the formation of mRNA granules. Expression of TcUBP1 truncated forms revealed the requirement of both N and C-terminal glutamine-rich low complexity sequences for the development of the drop-like phenotype in early-log epimastigotes. We propose that a rise in TcUBP1 levels, in synchrony with nutritional deficiency, can promote the differentiation of T. cruzi epimastigotes into infective metacyclic trypomastigotes.
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PMID:Translational repression by an RNA-binding protein promotes differentiation to infective forms in Trypanosoma cruzi. 2986 62