Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:3.1.27.1 (RNase)
 16,360 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Hel-NI and HuD belong to the elav gene family and have gained recent attention as potential neuroendocrine markers for small-cell lung carcinoma (SCLC). Members of this conserved family normally appear at different stages of neuronal maturation, raising the possibility that their expression patterns in SCLC reflect the degree of neuroendocrine differentiation. I have utilized a ribonuclease protection assay to analyze Hel-NI and HuD expression in cultured SCLC cells with high (classic phenotype) and low (variant phenotype) levels of neuroendocrine differentiation. Hel-NI was detected in both classic and variant SCLC. Although HuD was detected consistently in classic SCLC, it was low to absent in variant SCLC, indicating a significant down-regulation in that phenotype. The expression patterns of Hel-NI and HuD also were analyzed in 9 primary SCLC and 10 non-SCLC lung-tumor samples. In the majority of SCLC samples, either Hel-NI or HuD was detected exclusively or predominantly, indicating a pattern of variable gene expression similar to cultured SC LC. Neither transcript could be detected in the non-SCLC samples. These data indicate that (i) HuD mRNA expression is associated with a higher level of neuroendocrine differentiation in SCLC, (ii) Hel-NI and HuD expressions are variable in both primary and cultured SCLC and (iii) HuD and Hel-NI, in combination, are neurogenetic markers for SCLC.
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PMID:Differential expression of the neuroendocrine genes Hel-N1 and HuD in small-cell lung carcinoma: evidence for down-regulation of HuD in the variant phenotype. 929 25

We have isolated the gene that encodes the neural-specific RNA binding protein HuD in the mouse (Elavl4), and have mapped its location to the mid-distal region of chromosome 4, close to the neurological mutant clasper. The coding region of the Elavl4 gene covers approximately 44 kb; the first two RNA binding domains (RBDs) that are homologous to the two RBDs found in the Drosophila sex-lethal gene are each encoded in two exons, whereas the third RBD is encoded in a single exon. Elavl4 mRNAs are alternatively spliced in the region between RBDs 2 and 3 due to the variable use of two micro-exons, and RNase protection analysis indicates that two of four possible splice variants are the predominant isoforms expressed in the central nervous system. The high degree of sequence conservation between the Hu proteins suggests that the exon organization of all the Hu protein genes will be similar, if not identical, to the Elavl4 gene.
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PMID:Gene organization and chromosome location of the neural-specific RNA binding protein Elavl4. 952 51

The expression of mRNA for the neuronal antigen HuD (Elavl4) associated with paraneoplastic encephalomyelitis and sensory neuronopathy was evaluated in the developing and adult rat nervous system. Using RNase protection assay and non-radioactive in situ hybridization histochemistry HuD expression was shown to be expressed at high levels at the earliest time point observed (E15), but declined significantly during the first postnatal week to levels which were maintained into adulthood. In the adult, HuD expression became restricted primarily to large pyramidal-like neurons. Exceptions of note were many smaller neurons within a variety of thalamic nuclei. Expression of HuD was observed to be coincident with terminal differentiation of all neuronal structures evaluated regardless of the timing of their development, providing correlative evidence for a role in neuronal differentiation or the maintenance of neuronal phenotype. The marked restriction of HuD mRNA expression with maturity suggests that its functional role in adult neurons varies significantly throughout the CNS.
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PMID:Expression of mRNA for the elav-like neural-specific RNA binding protein, HuD, during nervous system development. 972 24

Hel-N1 and HuD belong to the elav gene family and encode neuron-specific RNA-binding proteins that are temporally regulated in neural development. Recently, these genes have been detected in small cell lung carcinoma, a neuroendocrine tumor, with HuD down-regulated in poorly differentiated, variant subsets. We, therefore, sought to determine: (a) the extent to which Hel-N1 and HuD are expressed in neuroblastoma (NB); and (b) whether the individual patterns of expression are associated with clinical features of the tumor. We used a sensitive and quantitative RNase protection assay that reliably distinguishes between these homologous genes, and with it we show that Hel-N1 and HuD transcripts were detected in 100% of cultured cells (11 of 11) and 97% of primary tumor samples (35 of 36). Densitometric quantification of transcripts indicated that the levels of HuD and Hel-N1 varied in all samples. In primary NB tissue, samples that expressed the highest Hel-N1 or HuD levels were N-myc unamplified. With HuD, the level in unamplified primary tumors was significantly higher than that of amplified tumors (0.80 +/- 0.12 versus 0.33 +/- 0.12, P < 0.02). HuD expression in prognostically favorable tumor stages was also significantly higher than unfavorable stages (0.98 +/- 0.19 versus 0.47 +/- 0.08, P < 0.03). In summary, the ubiquitous detection of HuD and Hel-N1 in NB indicates that they are molecular neuronal markers of this tumor. Furthermore, high HuD mRNA levels may predict a clinically favorable outcome.
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PMID:Neuron-specific hel-N1 and HuD as novel molecular markers of neuroblastoma: a correlation of HuD messenger RNA levels with favorable prognostic features. 981 74

Neuroserpin is an axonally secreted serine protease inhibitor expressed in the nervous system that protects neurons from ischemia-induced apoptosis. Mutant neuroserpin forms have been found polymerized in inclusion bodies in a familial autosomal encephalopathy causing dementia, or associated with epilepsy. Regulation of neuroserpin expression is mostly unknown. Here we demonstrate that neuroserpin mRNA and the RNA-binding protein HuD are co-expressed in the rat central nervous system, and that HuD binds neuroserpin mRNA in vitro with high affinity. Gel-shift, supershift and T1 RNase assays revealed three HuD-binding sequences in the 3'-untranslated region (3'-UTR) of neuroserpin mRNA. They are AU-rich and 20, 51 and 19 nt in length. HuD binding to neuroserpin mRNA was also demonstrated in extracts of PC12 pheochromocytoma cells. Additionally, ectopic expression of increasing amounts of HuD in these cells results in the accumulation of neuroserpin 3'-UTR mRNA. Furthermore, stably transfected PC12 cells over-expressing HuD contain increased levels of both neuroserpin mRNAs (3.0 and 1.6 kb) and protein. Our results indicate that HuD stabilizes neuroserpin mRNA by binding to specific AU-rich sequences in its 3'-UTR, which prolongs the mRNA lifetime and increases protein level.
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PMID:HuD binds to three AU-rich sequences in the 3'-UTR of neuroserpin mRNA and promotes the accumulation of neuroserpin mRNA and protein. 1200 Aug 40

The expression of the major protein kinase C substrate MARCKS (myristoylated alanine-rich C kinase substrate) is controlled by the stability of its mRNA. While the MARCKS mRNA is long living in quiescent fibroblasts (t1/2 = 14 h), its half-life time is drastically reduced (t1/2 = 2 h) in cells treated with phorbol esters to activate protein kinase C (PKC) or treated with growth factors. In a first step to study the underlying mechanism we identified both a cis-element on the MARCKS mRNA and the corresponding trans-acting factors. Fusing the complete 3'-UTR or specific regions of the 3'-UTR of the MARCKS gene to a luciferase reporter gene caused a drastic decrease in luciferase expression to as low as 5-10% of controls. This down-regulation was a result of destabilization of the chimeric transcript as shown by RNA run-off and Northern blot-assays. By RNase/EMSA and UV-cross-linking experiments, we identified a stretch of 52 nucleotides [(CUUU)11(U)8] in the 3'-UTR of the MARCKS mRNA specifically recognized by two RNA-binding proteins, HuD and HuR. These trans-acting factors are members of the ELAV gene family and bind the MARCKS CU-rich sequence with high affinity. Overexpression of HuD and HuR in murine fibroblasts caused a striking stabilization of the endogenous MARCKS mRNA even under conditions when the MARCKS mRNA is normally actively degraded, i.e. after treating cells with phorbol ester. These data imply, that the identified CU-rich cis-element of the MARCKS 3'-UTR is involved in conferring instability to mRNAs and that members of the ELAV gene family oppose this effect. Based on its structural and functional properties, the (CUUU)11(U)8 sequence described here can be grouped into class III of AU-rich elements.
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PMID:The 3'-UTR of the mRNA coding for the major protein kinase C substrate MARCKS contains a novel CU-rich element interacting with the mRNA stabilizing factors HuD and HuR. 1260 86