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)

During the early period of infection, the 4.9 kb (kb = 10(3) bases) E2A premRNA of adenovirus serotype 2 is matured mainly into a 2.0 kb mRNA by excision of introns of 2233 and 626 nucleotides. In order to define all the possible steps of splicing occurring in vivo, we characterized splicing intermediates present after a limiting treatment of cells with cycloheximide. Three complementary methods of analysis were used: RNA transfer analysis, S1 nuclease mapping and complementary DNA-RNase assay. Our principal conclusions concerning the poly(A)+ species are as follows. The RNA intermediate family detected is more complex than expected, since two major RNA intermediates of 4.6 kb and 4.3 kb, two minor intermediates of 2.9 kb and 2.6 kb, and a 2.3 kb RNA, which represents a minor alternative mRNA form, are revealed. Despite its large size and the presence of multiple internal donor and acceptor signals, intron 1 is exclusively excised as a whole. Intron 2 is either primarily excised as a whole, removing the standard 626-nucleotide sequence, or a smaller sequence of 337 nucleotides is removed, generating the 2.3 kb alternative mRNA. Kinetics of the ligation reaction demonstrate that the minimal time for excision of intron 2 is no more than two minutes, indicating a high level of co-ordination of the multiple individual reactions occurring during excision of an intron. Besides the major pathway for E2A premRNA splicing, namely the excision first of intron 2, followed by the excision of intron 1 after a lag time of five minutes, a minor pathway (used with a frequency of 10%) can be detected where the order of intron excision was inverted. With the alternative variant of excision of intron 2, at least three different pathways are therefore used to mature the E2A premRNA. RNA intermediates resulting from the cleavage at the 5' end of introns and branching can be detected by S1 mapping experiments, but their low accumulative level (1% relatively to the initial premRNA) precluded their direction by RNA transfer experiments and their complete characterization.
 ...
PMID:Splicing of the E2A premessenger RNA of adenovirus serotype 2. Multiple pathways in spite of excision of the entire large intron. 300 32

The mouse ME1 gene (HEB, REB and GE1, homologues in human, rat and chick, respectively) is a member of the nontissue-specific helix-loop-helix (HLH) gene family that includes E2A, E2-2 and Drosophila daughterless. We have examined the factors that control ME1 gene expression. ME1 is a single copy gene that spans > or = 150 kb of DNA and contains > 10 exons. Transcription was directed by an unusual initiator element that contained a 13 bp poly d(A) tract flanked by palindromic and inverted repeat sequences. Both RNase protection and primer extension analyses mapped the ME1 transcriptional start site to the center of the 13 bp poly d(A) tract. The ME1 initiator and its proximal sequences were required for promoter activity, supported basal levels of transcription, and contributed to cell type-specific gene expression. Other cis-elements utilized by the TATA-less ME1 promoter included a cluster of Sp1 response elements, E-boxes and a strong repressor. Collectively, our results suggest that the ME1 initiator and other cis-elements in the proximal promoter play an important role in regulating ME1 gene expression.
 ...
PMID:A novel initiator regulates expression of the nontissue-specific helix-loop-helix gene ME1. 778 73

The Grg gene encodes a 197-amino-acid protein homologous to the amino-terminal domain of the product of the groucho gene of the Drosophila Enhancer of split complex. We describe here the genomic organization of the mouse Grg gene. It spans approximately 7 kb on chromosome 10 and consists of seven exons. The 3' region of the Grg gene contains two functional polyadenylation sites that give rise to two transcripts that are differentially expressed among adult mouse tissues. The promoter region is very GC rich and lacks TATA box and "initiator" sequences. Primer extension analysis and ribonuclease protection assays show that Grg has a major transcription start site situated down-stream of putative binding motifs for the transcription factors Sp1, E2A, and PuF.
 ...
PMID:Genomic organization, alternative polyadenylation, and chromosomal localization of Grg, a mouse gene related to the groucho transcript of the Drosophila Enhancer of split complex. 791 24

Human T-cell lymphotropic virus type 1 (HTLV-1) is associated with adult T-cell leukemia (ATL) and HTLV-1-associated myelopathy/tropical spastic paraparesis (HAM/TSP). T-cell transformation is mainly due to the actions of the viral phosphoprotein Tax. Tax interacts with multiple transcriptional factors, aiding the transcription of many cellular genes. Here, we report that the cyclin-dependent kinase inhibitor p21/waf1 is overexpressed in all HTLV-1-infected cell lines tested as well as in ATL and HAM/TSP patient samples. Tax was found to be able to transactivate the endogenous p21/waf1 promoter, as detected by RNase protection, as well as activate a series of wild-type and 5'-deletion constructs linked to a luciferase reporter cassette. Wild-type but not a mutant form of Tax (M47) transactivated the p21/waf1 promoter in a p53-independent manner and utilized a minimal promoter that contained E2A and TATA box sequences. The p21/waf1 protein was reproducibly observed to be complexed with cyclin A/cdk2 and not with any other known G(1), S, or G(2)/M cyclins. Functionally, the association of p21/cyclin A/cdk2 decreased histone H1 phosphorylation in vitro, as observed in immunoprecipitations followed by kinase assays, and affected other substrates, such as the C terminus of Rb protein involved in c-Abl and histone deacetylase-1 (HDAC1) regulation. Interestingly, upon the use of a stress signal, such as gamma-irradiation, we found that the p21/cyclin A/cdk2 complex was able to block all known phosphorylation sites on the Rb molecule. Finally, using elutriated cell cycle fractions and a stress signal, we observed that the HTLV-1-infected T cells containing wild-type Tax, which had been in early or mid-G(1) phase prior to gamma-irradiation, arrested in G(1) and did not undergo apoptosis. This may be an important mechanism for an oncogenic virus such as HTLV-1 to stop the host at the G(1)/S boundary and to repair the damaged DNA upon injury, prior to S-phase entry.
 ...
PMID:Overexpression of p21(waf1) in human T-cell lymphotropic virus type 1-infected cells and its association with cyclin A/cdk2. 1090 81

Leptin is a 16-kDa hormone with an array of biologic actions. We, and others, have demonstrated that leptin is critical to the development of liver fibrogenesis both in vitro and in the lean littermates of ob/ob mice exposed to carbon tetrachloride (CCl(4)). Controversy exists as to whether leptin can act as a direct cytokine in the development of increased collagen expression, and whether ob/ob mice are resistant to potential injury from CCl(4). Here, we provide evidence that strongly suggests that leptin acts to increase nascent production of mRNA for the alpha2(I) collagen gene based upon ribonuclease protection analysis (RPA). Actinomycin D, but not cyclohexamide, or the pan-neutralizing antibody to transforming growth factor beta one (TGFbeta1), significantly diminished the effect of leptin on total alpha2(I) collagen mRNA levels. Further evidence that leptin acts directly on HSCs to alter gene expression in liver wounding is demonstrated by enhanced binding of phosphorylated signal transduction and activator of transcription factor 3 (pStat3) to a cis-inducible element (SIE) oligonucleotide by electrophoretic mobility shift assay (EMSA). This consensus sequence is responsible for production of a critical collagen transcription factor, AP-1. Finally, we have demonstrated from the ob/ob mouse model that these animals are at least as sensitive to CCl(4) as their respective lean animals as assessed by serum alanine aminotransferase (ALT) measurements. Taken together, the current data provide a continued framework that leptin is a profibrogenic cytokine and plays a key role in liver fibrosis.
 ...
PMID:Leptin induces increased alpha2(I) collagen gene expression in cultured rat hepatic stellate cells. 1270 94