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At least 667 records · Page 37Linked to original sources
PubMed1997

Response to interferon of GB virus C and hepatitis C virus in patients with chronic hepatitis.

OBJECTIVES: To evaluate the response to interferon and capacity to induce liver disease of a putative non-A to E hepatitis virus designated GB virus C (GBV-C). METHODS: RNA of GBV-C was detected by reverse transcription polymerase chain reaction with nested primers deduced from the 5'-noncoding region. It was titrated, along with RNA of hepatitis C virus (HCV), in 16 co-infected patients (11%) out of 140 patients who received interferon. RESULTS: At the completion of a 6-month course of interferon (total dose: 516-774 million units), GBV-C RNA disappeared from serum in seven (44%) and HCV RNA from serum in 11 (69%) patients. At 6 months after interferon treatment ended, GBV-C RNA remained cleared in three patients (19%), and HCV RNA was persistently undetectable in four (25%). One patient lost both GBV-C and HCV RNAs. The three patients whose serum was cleared of GBV-C RNA had pretreatment titers of the virus (two with 10[1]/ml and one with 10[2]/ml) that were considerably lower than the titers of 13 patients (one with 10[2]/ml, eight with 10[3]/ml, and four with > or = 10[4]/ml) without such clearance. The decrease in alanine aminotransferase levels paralleled the response of HCV RNA but not that of GBV-C RNA to interferon. The response of HCV at 6 months after interferon in the co-infected patients (4/16 or 25%) did not differ significantly from that in patients without GBV-C infection (44/124 or 35%). CONCLUSIONS: The sensitivity of GBV-C to interferon is comparable to but independent of HCV. Co-infection with GBV-C does not influence the response to interferon of patients with chronic hepatitis C.

Antiviral Agents↗
PubMed2006

Argonaute--a database for gene regulation by mammalian microRNAs.

MicroRNAs (miRNAs) constitute a recently discovered class of small non-coding RNAs that regulate expression of target genes either by decreasing the stability of the target mRNA or by translational inhibition. They are involved in diverse processes, including cellular differentiation, proliferation and apoptosis. Recent evidence also suggests their importance for cancerogenesis. By far the most important model systems in cancer research are mammalian organisms. Thus, we decided to compile comprehensive information on mammalian miRNAs, their origin and regulated target genes in an exhaustive, curated database called Argonaute (http://www.ma.uni-heidelberg.de/apps/zmf/argonaute/interface). Argonaute collects latest information from both literature and other databases. In contrast to current databases on miRNAs like miRBase::Sequences, NONCODE or RNAdb, Argonaute hosts additional information on the origin of an miRNA, i.e. in which host gene it is encoded, its expression in different tissues and its known or proposed function, its potential target genes including Gene Ontology annotation, as well as miRNA families and proteins known to be involved in miRNA processing. Additionally, target genes are linked to an information retrieval system that provides comprehensive information from sequence databases and a simultaneous search of MEDLINE with all synonyms of a given gene. The web interface allows the user to get information for a single or multiple miRNAs, either selected or uploaded through a text file. Argonaute currently has information on 839 miRNAs from human, mouse and rat.

Animals↗
PubMed1995

Growth hormone (GH) receptor and GH-binding protein messenger ribonucleic acids with alternative 5'-untranslated regions are differentially expressed in mouse liver and placenta.

Two 5'-untranslated regions (5'UTRs) with distinctly different sequences, designated 5'UTR L1 and 5'UTR L2, were obtained by amplification of complementary DNA from mouse liver and placenta with primers complementary to sequences from the hormone-binding domain common to GH receptor (GHR) and GH-binding protein (GHBP) messenger RNAs (mRNAs). The presence of an open reading frame in the 5'UTR L2 and the high GC content of this sequence suggest that mRNAs containing this 5'UTR may be translated with a lower efficiency than those containing 5'UTR L1. Expression studies showed that 5'UTR L1 and 5'UTR L2 are present in GHR and GHBP mRNAs in both tissues. However, the relative expression of the two 5'UTRs differs between liver and placenta and in liver from different physiological states. The different expression patterns of the L1 and L2 5'UTRs predict that the corresponding 5'-noncoding exons of the GHR/GHBP gene are associated with different regulatory elements. The expression patterns of the 5'UTRs also indicate that there is a linkage between the 5'UTR present in GHR/GHBP gene transcripts and the alternative splicing of these transcripts to yield either GHR or GHBP mRNAs. The 5'-noncoding exon used for transcription of the GHR/GHBP gene, therefore, may be involved in regulating both the ratio of GHR to GHBP transcripts and the efficiency of translation of these transcripts. Transcription from the different 5'-noncoding exons of the GHR/GHBP gene thus may be a critical element in the regulation of the expression of GHR and GHBP and thereby in the control of the responses of different tissues to GH.

Alternative Splicing↗
PubMed2006

Non-coding RNA in fly dosage compensation.

Dosage compensation modulates global expression of an X chromosome and is necessary to restore the balance between X-chromosome and autosome expression in both sexes. A central question in the field is how this regulation is directed. Large non-coding RNAs, such as Xist in mammals and roX in flies, have pivotal roles in targeting chromosome-wide modification for dosage compensation. Several recent studies in Drosophila provide new insight into the principles of X-chromosome recognition and the function of non-coding RNA in this process.

Animals↗
PubMed1990

Most of the homeobox-containing Xhox 36 transcripts in early Xenopus embryos cannot encode a homeodomain protein.

Multiple Xhox 36 transcripts accumulate in Xenopus embryos from gastrula to early tadpole stages. The transcripts were characterized by sequencing cDNA clones and by S1 protection and Northern (RNA) blotting of embryonic RNA with probes derived from the cDNAs. The Xhox 36 RNAs included unspliced precursor transcripts that accumulated in the embryonic nuclei, spliced transcripts that contained multiple stop codons in frame with the homeobox, and less abundant coding mRNAs. These transcripts were generated either by alternative splicing or multiple initiations from a single Xhox 36 gene. The sequence of a cDNA clone of the unspliced transcript showed that the intron contained a noncanonical 3' splice site. However, the intron was spliced efficiently when expressed from a plasmid injected into Xenopus embryos, suggesting that the inefficient splicing of the endogenous RNA is not due to the unusual 3' splice site. The accumulation of noncoding and unspliced transcripts suggests multiple levels of regulation in the embryonic expression of the Xhox 36 gene.

Animals↗
PubMed1991

The rodent B2 sequence can affect expression when present in the transcribed region of a reporter gene.

The mouse B2 element is a moderately repetitive nt sequence of 180 bp transcribed by RNA polymerase III (Pol III) at high levels in embryonic and transformed cells. The B2 sequence is present in either orientation within the noncoding regions of a number of genes transcribed by RNA polymerase II (Pol II). We sought to determine if the small B2 transcripts generated by Pol III are natural antisense RNA molecules which might hybridize to complementary sequences present within Pol II transcripts. Chimaeric reporter genes encoding Escherichia coli gpt were constructed containing a B2 repeat in either orientation within the 5'- or 3'-untranslated regions. These constructs were transfected into embryonal carcinoma (EC) cells and expression of the reporter gene was analysed in EC cells and retinoic acid-treated EC cells, which contain high and low levels of small B2 RNAs, respectively. Although the B2 sequences affected expression of the reporter gene, these effects did not appear to be due to hybridization of the small B2 RNA to the reporter transcripts. The presence of B2 sequences near a Pol II-transcribed gene can alter expression of that gene in a position- and orientation-dependent manner, suggesting these repetitive elements may be cis-acting regulators of gene expression.

Animals↗
PubMed1995

Interaction of polypyrimidine tract-binding protein with the 5' noncoding region of the hepatitis C virus RNA genome and its functional requirement in internal initiation of translation.

Initiation of translation of the human hepatitis C virus (HCV) RNA genome occurs by internal ribosome entry into the 5' noncoding region (5'NCR) in a cap-independent manner. The internal ribosome entry site of the HCV 5'NCR has been previously defined to encompass almost the entire 5'NCR. Here we report the interaction of polypyrimidine tract-binding protein (PTB) at three distinct regions within the 5'NCR by UV cross-linking assays. All three regions contain a consensus polypyrimidine tract motif. The evidence for the interaction of recombinant PTB at multiple sites within the 5'NCR is based on the use of 5'NCR mutants as competitors and by direct UV cross-linking of the mutant RNAs. Furthermore, the PTB isomers from HeLa nuclear extracts interact with the HCV 5'NCR, as shown by immunoprecipitation of a UV cross-linked complex with anti-PTB serum. Immunodepletion of PTB from translation lysates suggested the functional requirement for PTB during translation initiation of the HCV RNA. Addition of purified PTB to immunodepleted lysates did not restore translation mediated by the HCV 5'NCR, indicating the requirement of PTB-associated factors that were removed during immunodepletion.

Base Sequence↗
PubMed1999

Collection of mRNA-like non-coding RNAs.

In last few years much data has accumulated which shows that in different cells various RNA transcripts are synthesized. They lack protein coding capacity and do not produce mature protein. It seems that they work mainly or exclusively on the RNA level. Their function and mechanism of action is poorly understood. In this paper we have collected all known RNA transcript and prepared a database for further structural and functional studies. This is the first collection of the nucleotide sequences of RNAs of this kind. The data can be accessed via WWW at: http://www.man.poznan.pl/5SData/ncRNA/inde x.html

Animals↗
PubMed1982

Expression of the ROAM mutations in Saccharomyces cerevisiae: involvement of trans-acting regulatory elements and relation with the Ty1 transcription.

The regulatory mutations in Saccharomyces cerevisiae designated cargA + Oh, cargB + Oh, and durOh are alterations in the control regions of the respective structural genes. The alteration causing the cargA + Oh mutation has been shown to be an insertion of a Ty1 element in the 5' noncoding region of the CAR1 ( cargA ) locus. All three mutations cause overproduction of their corresponding gene products and belong to the ROAM family of mutations (Regulated Overproducing Allele responding to Mating signals) in yeast. The amount of overproduction in ROAM mutants is determined, at least in part, by signals that control mating functions in yeast. We report the identification of two genetic loci that regulate Oh mutant gene expression but that do not affect mating ability. These loci are defined by the recessive roc mutations ( ROAM mutation control) that reduce the amount of overproduction caused by the cargA + Oh, cargB + Oh, and durOh mutations. RNAs homologous to CAR1 ( cargA ), DUR1 ,2 and Ty1 DNA probes were analyzed by the Northern hybridization technique. In comparison with wild-type strains, cargA + Oh and durOh mutant strains grown on ammonia medium contain increased amounts of CAR1 and DUR1 ,2 RNA. This RNA overproduction is diminished in MATa/MAT alpha diploid strains as well as in haploid strains that also carry the ste7 mutation which prevents mating or that carry either of the roc1 or roc2 mutant alleles. The amount of RNA homologous to Ty1 DNA is also reduced in ste7 , roc1 , and roc2 mutant strains. This reduction is not observed in a strain with the ste5 mutation, which prevents mating but has no effect on overproduction of ROAM mutant gene products.(ABSTRACT TRUNCATED AT 250 WORDS)

Allophanate Hydrolase↗
PubMed1986

Heart myosin light chain 2 gene. Nucleotide sequence of full length cDNA and expression in normal and hypertensive rat.

We have isolated and characterized a cDNA recombinant plasmid (pRLC429) specific for the rat heart myosin light chain 2 (MLC2). The cDNA insert consists of 446 base pairs, including a 72-base pair segment of the 3'-untranslated region. Additional 5'-sequence, not present in plasmid pRLC429, was obtained by primer extension of the cDNA. The extended cDNA sequence combined with the plasmid pRLC429 sequence provided the codon information for the entire MLC2 polypeptide and partial sequences for the 3'- and 5'-noncoding regions of MLC2 mRNA. The predicted amino acid sequence for rat heart MLC2 showed a high homology with the sequences available for the chicken (83%) and human heart (80%) MLC2s. However, the homology between rat heart MLC2 and its counterpart in rat skeletal muscle is relatively low (67%). On the basis of the nuclease S1 protection assay with uniformly labeled single-stranded pRLC429 DNA, subcloned into M13mp18 phage vector, we conclude that the rat atrial muscle also contains MLC2 of the ventricular type. In an attempt to ascertain whether structural variants of MLC2 are expressed in hypertrophic heart muscle, we examined the RNAs from spontaneously hypertensive rat where there is a natural progression of hypertrophy associated with an increase in blood pressure. The RNA isolated from 7-, 13-, and 18-week-old spontaneously hypertensive rat hearts protected the same length DNA against S1 nuclease as was observed with RNAs from the age-matched normal rat hearts, suggesting that there is a single MLC2 gene transcript expressed in both the normal and hypertrophic heart muscle cells.

Amino Acid Sequence↗
PubMed2003

RNAs templating chromatin structure for dosage compensation in animals.

The role of RNA as a messenger in the expression of the genome has been long appreciated, but its functions in regulating chromatin and chromosome structure are no less interesting. Recent results have shown that small RNAs guide chromatin-modifying complexes to chromosomal regions in a sequence-specific manner to elicit transcriptional repression. However, sequence-specific targeting by means of base pairing seems to be only one mechanism by which RNA is employed for epigenetic regulation. The focus of this review is on large RNAs that act in the dosage-compensation pathways of flies and mammals. These RNAs associate with chromatin over the length of whole chromosomes and are crucial for spreading epigenetic changes in chromatin structure. They do not appear to act in a sequence-specific manner but might provide scaffolds for co-operative binding of chromatin-associated complexes that enable spreading of chromatin modifications.

Animals↗
PubMed2024

Whole transcriptome sequencing analyses of islets reveal ncRNA regulatory networks underlying impaired insulin secretion and increased β-cell mass in high fat diet-induced diabetes mellitus.

AIM: Our study aims to identify novel non-coding RNA-mRNA regulatory networks associated with β-cell dysfunction and compensatory responses in obesity-related diabetes. METHODS: Glucose metabolism, islet architecture and secretion, and insulin sensitivity were characterized in C57BL/6J mice fed on a 60% high-fat diet (HFD) or control for 24 weeks. Islets were isolated for whole transcriptome sequencing to identify differentially expressed (DE) mRNAs, miRNAs, IncRNAs, and circRNAs. Regulatory networks involving miRNA-mRNA, lncRNA-mRNA, and lncRNA-miRNA-mRNA were constructed and functions were assessed through Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses. RESULTS: Despite compensatory hyperinsulinemia and a significant increase in β-cell mass with a slow rate of proliferation, HFD mice exhibited impaired glucose tolerance. In isolated islets, insulin secretion in response to glucose and palmitic acid deteriorated after 24 weeks of HFD. Whole transcriptomic sequencing identified a total of 1324 DE mRNAs, 14 DE miRNAs, 179 DE lncRNAs, and 680 DE circRNAs. Our transcriptomic dataset unveiled several core regulatory axes involved in the impaired insulin secretion in HFD mice, such as miR-6948-5p/Cacna1c, miR-6964-3p/Cacna1b, miR-3572-5p/Hk2, miR-3572-5p/Cckar and miR-677-5p/Camk2d. Additionally, proliferative and apoptotic targets, including miR-216a-3p/FKBP5, miR-670-3p/Foxo3, miR-677-5p/RIPK1, miR-802-3p/Smad2 and ENSMUST00000176781/Caspase9 possibly contribute to the increased β-cell mass in HFD islets. Furthermore, competing endogenous RNAs (ceRNA) regulatory network involving 7 DE miRNAs, 15 DE lncRNAs and 38 DE mRNAs might also participate in the development of HFD-induced diabetes. CONCLUSIONS: The comprehensive whole transcriptomic sequencing revealed novel non-coding RNA-mRNA regulatory networks associated with impaired insulin secretion and increased β-cell mass in obesity-related diabetes.

Mice↗
PubMed1983

Transcriptional analysis of the Saccharomyces cerevisiae mitochondrial var1 gene: anomalous hybridization of RNA from AT-rich regions.

A family of mitochondrial RNAs hybridizes specifically to the var1 region on Saccharomyces cerevisiae mitochondrial DNA (Farrelly et al., J. Biol. Chem. 257:6581-6587, 1982). We constructed a fine-structure transcription map of this region by hybridizing DNA probes containing different portions of the var1 region and some flanking sequences to mitochondrial RNAs isolated from var1-containing petites. We also report the nucleotide sequence of more than 1.2 kilobases of DNA flanking the var1 gene. Our primary findings are: (i) The family of RNAs we detect with homology to var1 DNA is colinear with the var1 gene. Their direction of transcription is olil to cap, as it is for most other mitochondrial genes. (ii) Extensive hybridization anomalies are present, most likely due to the high A-T (A-U) content of the hybridizing species and to the asymmetric distribution of their G-C residues. An important conclusion is that failure to detect transcripts from A-T-rich regions of the yeast mitochondrial genome by standard blot transfer hybridizations cannot be interpreted to mean that such sequences, which are commonly supposed to be spacer DNA, are noncoding or lack direct function in the expression of mitochondrial genes.

Base Composition↗
PubMed1991

Genetic analysis of porcine respiratory coronavirus, an attenuated variant of transmissible gastroenteritis virus.

The genome and transcriptional pattern of a newly identified respiratory variant of transmissible gastroenteritis virus were analyzed and compared with those of classical enterotropic transmissible gastroenteritis virus. The transcriptional patterns of the two viruses indicated that differences occurred in RNAs 1 and 2(S) and that RNA 3 was absent in the porcine respiratory coronavirus (PRCV) variant. The smaller RNA 2(S) of PRCV was due to a 681-nucleotide (nt) deletion after base 62 of the PRCV peplomer or spike (S) gene. The PRCV S gene still retained information for the 16-amino-acid signal peptide and the first 6 amino acid residues at the N terminus of the mature S protein, but the adjacent 227 residues were deleted. Two additional deletions (3 and 5 nt) were detected in the PRCV genome downstream of the S gene. The 3-nt deletion occurred in a noncoding region; however, the 5-nt deletion shortened the potential open reading frame A polypeptide from 72 to 53 amino acid residues. Significantly, a C-to-T substitution was detected in the last base position of the transcription recognition sequence upstream of open reading frame A, which rendered RNA 3 nondetectable in PRCV-infected cell cultures.

Base Sequence↗
PubMed2006

Microarray analysis of RNA processing and modification.

Most RNAs are processed from precursors by mechanisms that include covalent modifications, as well as the removal of flanking and intervening sequences. Traditional methods to detect RNA processing, such as Northern blotting, reverse-transcribed polymerase chain reaction and primer extension assays, are difficult to apply on a large scale. This chapter outlines several methods for analysis of the processing and modification of RNA using microarrays. These encompass protocols for the application of homemade microarrays and custom-designed commercial inkjet microarrays and are tailored for the large-scale analysis of processing of mRNA, including alternative splicing, as well as for the analysis of processing and modification of noncoding RNA. This chapter also describes practical aspects of microarray design, sample preparation, hybridization, and data analysis.

Animals↗
PubMed1999

Specific interaction of a 25-kilodalton cellular protein, a 40S ribosomal subunit protein, with the internal ribosome entry site of hepatitis C virus genome.

Translation initiation of hepatitis C virus (HCV) RNA is controlled by an internal ribosome entry site (IRES) contained in 5' noncoding region (NCR) and in several nucleotides of the coding region. The ability of a 25-kilodalton cellular protein (p25) to bind the HCV 5' NCR is correlated with the efficiency of translation initiation of HCV RNA, indicating that this protein plays a critical role in HCV translation (S. Fukushi, C. Kurihara, N. Ishiyama, F. B. Hoshino, A. Oya, and K. Katayama, J Virol 71, 1662-1666, 1997). We have extended the study for identification of the IRES region required for p25 binding. For this purpose, we have performed UV cross-linking competition analyses using 5'- or 3'- deleted mutants of the HCV 5' NCR as competitor RNAs for binding of p25 to wild-type HCV 5' NCR. Competitor RNAs lacking nucleotides (nt) 47-74 or nt 279-331 did not inhibit p25 binding to the HCV IRES, indicating that these regions are necessary for interaction of the p25 and HCV IRES. Since p25 binding was not observed in the IRES elements of encephalomyocarditis virus and poliovirus in UV cross-linking competition analyses, the p25 binding may be specific for the HCV IRES. p25 bound to the HCV IRES was detected when a purified 40S ribosomal subunit was used for UV cross-linking experiment, indicating that p25 is one of 40S ribosomal subunit proteins. These results reveal an unique interaction between the 40S ribosomal subunit and HCV IRES to contribute to translation initiation of the HCV genome.

Base Sequence↗
PubMed1990

Polyomavirus late pre-mRNA processing: DNA replication-associated changes in leader exon multiplicity suggest a role for leader-to-leader splicing in the early-late switch.

Polyomavirus late mRNAs contain at their 5' ends multiple, tandem repeats of a 57-base noncoding sequence, the late leader, whose sequence appears only once in the viral genome. Pre-mRNA molecules are processed by a pathway that includes the splicing of late leader exons to each other in giant, multigenome-length precursors which are the result of inefficient transcription termination. We have devised a method involving reverse transcription and the polymerase chain reaction to determine the number of tandem late leader units on polyomavirus late RNA molecules. Using this technique, we have shown that each class of late viral mRNA (mVP1, mVP2, and mVP3) consists of molecules with between 1 and 12 tandem leader units at their 5' ends. Importantly, single-leader RNAs are underrepresented in both the cytoplasm and the nucleus, suggesting that single-leader primary transcripts are preferentially degraded in the nucleus. In addition, the average number of leaders on late RNAs increases in the presence of DNA replication. Taken together with previous work from our laboratory, the results presented here are consistent with a model for the control of late gene expression at the level of RNA splicing and stability which is in turn controlled by the efficiency of transcription termination.

Animals↗
PubMed1995

The L protein of Rift Valley fever virus can rescue viral ribonucleoproteins and transcribe synthetic genome-like RNA molecules.

Overlapping cDNAs representing the complete L segment of Rift Valley fever virus were assembled, and the L protein was expressed via a recombinant vaccinia virus. The transcriptase activity of the L protein was assayed with two types of templates: natural ribonucleoproteins (RNPs) and artificial genome-like RNAs. RNPs purified in a CsCl gradient did not retain the RNA polymerase function, but the activity was restored when the L cDNA was expressed in mammalian cells via a recombinant vaccinia virus. Indeed, after transfection of transcriptase-depleted RNPs in cells infected with the recombinant vaccinia virus expressing the L protein, the mRNAs coding for the N and NSs proteins and to a lesser extent, those coding for the glycoproteins were synthesized as well as the corresponding proteins. The transcriptase activity of the recombinant L protein was then investigated by using synthetic templates containing the reporter chloramphenicol acetyltransferase gene in the antisense orientation flanked by the 3' and 5' noncoding region of the S genomic segment. Our results indicate that after transfection of the RNA templates, transcription was achieved in cells coexpressing both the L and N proteins. Together, the experiments demonstrate that the two proteins N and L are absolutely required and sufficient to reconstitute the transcriptase activity.

Base Sequence↗