Search PubMed⌕ Search

Biomedical subjects

T Kiss

Publications and source records attributed to T Kiss.

At least 73 records · Page 4Linked to original sources

Sequence and structural elements of methylation guide snoRNAs essential for site-specific ribose methylation of pre-rRNA.

Site-specific 2'-O-ribose methylation of eukaryotic rRNAs is guided by small nucleolar RNAs (snoRNAs). The methylation guide snoRNAs carry long perfect complementaries to rRNAs. These antisense elements are located either in the 5' half or in the 3' end region of the snoRNA, and are followed by the conserved D' or D box motifs, respectively. An uninterrupted helix formed between the rRNA and the antisense element of the snoRNA, in conjunction with the adjacent D' or D box, constitute the recognition signal for the putative methyltransferase. Here, we have identified an additional essential box element common to methylation guide snoRNAs, termed the C' box. We show that the C' box functions in concert with the D' box and plays a crucial role in the methyltransfer reaction directed by the upstream antisense element and the D' box. We also show that an internal fragment of U24 methylation guide snoRNA, encompassing the upstream antisense element and the D' and C' box motifs, can support the site-specific methylation of rRNA. This strongly suggests that the C box of methylation guide snoRNAs plays an essential role in the methyltransfer reaction guided by the 3'-terminal antisense element and the D box of the snoRNA.

Base Sequence↗

Human U19 intron-encoded snoRNA is processed from a long primary transcript that possesses little potential for protein coding.

While exons were originally defined as coding regions of split eukaryotic genes, introns have long been considered as mainly noncoding "genetic junk." However, recognition that a large number of small nucleolar RNAs (snoRNAs) are processed from introns of pre-mRNAs demonstrated that introns may also code for functional RNAs. Moreover, recent characterization of the mammalian UHG gene that encodes eight box C/D intronic snoRNAs suggested that some genes generate functional RNA products exclusively from their intron regions. In this study, we show that the human U19 box H/ACA snoRNA, which is encoded within the second intron of the U19H gene, represents the only functional RNA product generated from the long U19H primary transcript. Splicing of the U19H transcript, instead of giving rise to a defined RNA, produces a population of diverse U19H RNA molecules. Although the first three exons of the U19H gene are preserved in each processed U19H RNA, the 3' half of the RNA is generated by a series of apparently random splicing events. Because the U19H RNA possesses limited potential for protein coding and shows a predominant nucleoplasmic localization, we suggest that the sole function of the U19H gene is to express the U19 intronic snoRNA. This suggests that, in marked contrast to our previous dogmatic view, genes generating functionally important RNAs exclusively from their intron regions are probably more frequent than has been anticipated.

Alternative Splicing↗

[Polysaccharides of Glycyrrhiza glabra L. and Glycyrrhiza echinata L. Medicinal plants II].

Comparative study was carried out among the polysaccharides of Chinese, Lithuanian and Hungarian origin Glycyrrhiza glabra root samples as well as the Hungarian origin Glycyrrhiza echinata, which has not been studied earlier. The plant material was extracted with boiling water and the yield, the carbohydrate and the uronic acid content was measured by the alpha-naphtol and the Bitter method [21], respectively. Although the yield of Hungarian origin species was found lower than the yield of eastern species, the uronic acid content was similar. (Table I.) Our results show that to extract polysaccharides containing uronic acids needed longer extraction time, about 4 hours. The stem of Glycyrrhiza echinata might be useful from a practical point of view because of its large size and easy of access. (Table I. II.) Some fractions containing uronic acid in higher amount were separated on DEAE Sepharose CL-6B anion exchange column. After hydrolysis, reduction and acetylation the monosaccharide composition of this fractions was analysed by GC. (Table IV.).

China↗

A small nucleolar RNP protein is required for pseudouridylation of eukaryotic ribosomal RNAs.

Eukaryotic rRNAs possess numerous post-transcriptionally modified nucleotides. The most abundant modifications, 2'-O-ribose methylation and pseudouridylation, occur in the nucleolus during rRNA processing. The nucleolus contains a large number of small nucleolar RNAs (snoRNAs) most of which can be classified into two distinct families defined by conserved sequence boxes and common associated proteins. The C and D box-containing snoRNAs are associated with fibrillarin, and most of them function as guide RNAs in site-specific ribose methylation of rRNAs. The nucleolar function of the other class of snoRNAs, which share box H and ACA elements and are associated with a glycine- and arginine-rich nucleolar protein, Gar1p, remains elusive. Here we demonstrate that the yeast Saccharomyces cerevisiae Gar1 snoRNP protein plays an essential and specific role in the overall pseudouridylation of yeast rRNAs. These results establish a novel function for Gar1 protein and indicate that the box H/ACA snoRNAs, or at least a subset of these snoRNAs, function in the site-specific pseudouridylation of rRNAs.

Alleles↗

Site-specific pseudouridine formation in preribosomal RNA is guided by small nucleolar RNAs.

During the nucleolar maturation of eukaryotic ribosomal RNAs, many selected uridines are converted into pseudouridine by a thus far undefined mechanism. The nucleolus contains a large number of small RNAs (snoRNAs) that share two conserved sequence elements, box H and ACA. In this study, we demonstrate that site-specific pseudouridylation of rRNAs relies on short ribosomal signal sequences that are complementary to sequences in box H/ACA snoRNAs. Genetic depletion and reconstitution studies on yeast snR5 and snR36 snoRNAs demonstrate that box H/ACA snoRNAs function as guide RNAs in rRNA pseudouridylation. These results define a novel function for snoRNAs and further reinforce the idea that base pairing is the most common way to obtain specific substrate-"enzyme" interactions during rRNA maturation.

Base Composition↗

The family of box ACA small nucleolar RNAs is defined by an evolutionarily conserved secondary structure and ubiquitous sequence elements essential for RNA accumulation.

Eukaryotic cells contain a large number of small nucleolar RNAs (snoRNAs). A major family of snoRNAs features a consensus ACA motif positioned 3 nucleotides from the 3' end of the RNA. In this study we have characterized nine novel human ACA snoRNAs (U64-U72). Structural probing of U64 RNA followed by systematic computer modeling of all known box ACA snoRNAs revealed that this class of snoRNAs is defined by a phylogenetically conserved secondary structure. The ACA snoRNAs fold into two hairpin structures connected by a single-stranded hinge region and followed by a short 3' tail. The hinge region carries an evolutionarily conserved sequence motif, called box H (consensus, AnAnnA). The H box, probably in concert with the flanking helix structures and the ACA box characterized previously, plays an essential role in the accumulation of human U64 intronic snoRNA. The correct processing of a yeast ACA snoRNA, snR36, in mammalian cells demonstrated that the cis- and trans-acting elements required for processing and accumulation of ACA snoRNAs are evolutionarily conserved. The notion that ACA snoRNAs share a common secondary structure and conserved box elements that likely function as binding sites for common proteins (e.g., GAR1) suggests that these RNAs possess closely related nucleolar functions.

Base Sequence↗

[Long-term experience with prophylactic BCG therapy of high risk patients with superficial bladder tumors].

The authors analysed the data of 45 high risk patients with recurrent superficial transitional cell cancer of the bladder who received after radical transurethral resection prophylactic intracavitaly BCG treatment among 1987-1995. They observed complete remission (28/45), partial remission (10/45), non responders (7/45). The progression rate was (12/45). In case of recurrence they made a second cure with high dose BCG. They deemed the maintenance therapy useful. They reviewed their experiences with the patients who had a B2 stage before. They gave account of their result after complementary chemotherapy with Pallagicin. One serious pulmonary side effect, was detected, which had been treated successfully with antituberculotic drugs.

Administration, Intravesical↗

[Multiple metastases of malignant cutaneous melanoma into the upper urinary tract].

The authors describe their case of the extremely rare multiple metastases of cutan melanoma malignum in the upper urinary tracts as it was treated with operations. In the case of their 17-year old patient first percutan resection of the right side of the renal pelvis-wall was done then one and half months later ureteronephrectomia was carried out on the right side because of metastases in the renal pelvis and the ureter. The primary tumour had been removed from the hairy area of the head 9 months earlier in a dermatological department. The authors have met only 14 similar cases in the international literature. In Hungary no review of any similar case has been found.

Adolescent↗

Effect of molluscan neuropeptide RAPYFVamide on identified Helix pomatia L. neurons.

1. The effect of Mytilus inhibitory peptide-related peptide RAPYFVamide, isolated from Helix pomatia brain, was studied on 21 different identified Helix neurons. 2. It was found that the neuropeptide hyperpolarized 11 of the 21 neurons studied, inducing a K-dependent current. Not all neurons responded by hyperpolarization to the peptide application, though, in all cases the voltage-dependent outward K and inward Ca currents were depressed. 3. This may show that, in the peptide effect, more than one type of K conductance is involved. 4. It is proposed that RAPYFVamide may have a functional role in the modulation of the feeding behavior in H. pomatia.

Amino Acid Sequence↗

Function and synthesis of small nucleolar RNAs.

Eukaryotic cells contain an extraordinarily complex population of small nucleolar RNAs (snoRNAs). During its brief lifetime, each human pre-rRNA molecule will transiently associate with approximately 150 different snoRNA species. In the past year our understanding of snoRNAs has been clarified by the recognition that the snoRNA population can be divided into a small number of groups which are structurally and functionally distinct. The two largest groups of snoRNAs direct the site-specific modification of the pre-rRNA at positions of 2'-O-methylation and pseudouridine formatio. Other groups of snoRNAs function in pre-rRNA cleavage and in the formation of the correct structure of the pre-rRNA.

Animals↗

Speciation of aluminum in biological systems.

As a "hard", trivalent metal ion, Al3- binds strongly to oxygen-donor ligands such as citrate and phosphate. The aqueous coordination chemistry of Al is complicated by the tendency of many Al complexes to hydrolyze and form polynuclear species, many of which are sparingly soluble. Thus there is considerable variation among the Al stability constants reported for several important ligands. The complexity in the aqueous chemistry of Al has also affected Al toxicity studies, which have often utilized poorly characterized Al stock solutions. Serum fractionation studies show that most Al is protein bound, primarily to the serum iron transport protein transferrin. Albumin appears to play little, if any, role in serum transport. There is little agreement as to the speciation of the remaining low-molecular mass fraction of serum Al. The lability of the Al3+ion precludes the simple separation and identification of individual Al complexes. Computational methods are available for detailed computer calculations of the Al speciation in serum, but efforts in this area have been severely hampered by the uncertainties regarding the stability constants of the low molecular mass Al complexes with citrate, phosphate, and hydroxide. Specific recommendations for further research on Al speciation include: (1) Determine more accurate Al stability constants with critical low molecular mass ligands such as citrate and phosphate; (2) supplement traditional potentiometric studies on Al complexes with data from other techniques such as 27Al-NMR and accelerator mass spectrometry with 26Al; (3) develop new methods for generating reliable linear free energy relationships for Al complexation; (4) determine equilibrium and rate constants for Al binding to transferrin at 37 degrees C; (5) confirm the possible formation of low-molecular-mass Al-protein complexes following desferrioxamine therapy; (6) continue research efforts to incorporate kinetic considerations into the present equilibrium speciation calculations; (7) improve methods for preparing chemically well-defined stock solutions for toxicological studies; (8) incorporate more detailed speciation data into studies on Al toxicity and pharmacokinetics; and (9) incorporate more detailed speciation data into future epidemiological studies on the relationship between Al toxicity and various water quality parameters.

Aluminum↗

Site-specific ribose methylation of preribosomal RNA: a novel function for small nucleolar RNAs.

Eukaryotic cells contain many fibrillarin-associated small nucleolar RNAs (snoRNAs) that possess long complementarities to mature rRNAs. Characterization of 21 novel antisense snoRNAs from human cells followed by genetic depletion and reconstitution studies on yeast U24 snoRNA provides evidence that this class of snoRNAs is required for site-specific 2'-O-methylation of preribosomal RNA (pre-rRNA). Antisense sno-RNAs function through direct base-pairing interactions with pre-rRNA. The antisense element, together with the D or D' box of the snoRNA, provide the information necessary to select the target nucleotide for the methyltransfer reaction. The conclusion that sno-RNAs function in covalent modification of the sugar moieties of ribonucleotides demonstrates that eukaryotic small nuclear RNAs have a more versatile cellular function than earlier anticipated.

Base Sequence↗

Characterization of the intron-encoded U19 RNA, a new mammalian small nucleolar RNA that is not associated with fibrillarin.

We have characterized a new member (U19) of a group of mammalian small nuclear RNAs that are not precipitable with antibodies against fibrillarin, a conserved nucleolar protein associated with most of the small nucleolar RNAs characterized to date. Human U19 RNA is 200 nucleotides long and possesses 5'-monophosphate and 3'-hydroxyl termini. It lacks functional boxes C and D, sequence motifs required for fibrillarin binding in many other snoRNAs. Human and mouse RNA are 86% homologous and can be folded into similar secondary structures, a finding supported by the results of nuclease probing of the RNA. In the human genome, U19 RNA is encoded in the intron of an as yet not fully characterized gene and could be faithfully processed from a longer precursor RNA in HeLa cell extracts. During fractionation of HeLa cell nucleolar extracts on glycerol gradients, U19 RNA was associated with higher-order structures of approximately 65S, cosedimenting with complexes containing 7-2/MRP RNA, a conserved nucleolar RNA shown to be involved in 5.8S rRNA processing in yeast cells.

Animals↗

Exonucleolytic processing of small nucleolar RNAs from pre-mRNA introns.

Many small nucleolar RNAs (snoRNAs) in vertebrates are encoded within introns of protein genes. We have reported previously that two isoforms of human U17 snoRNA are encoded in introns of the cell-cycle regulatory gene, RCC1. We have now investigated the mechanism of processing of U17 RNAs and of another intron-encoded snoRNA, U19. Experiments in which the processing of intronic RNA substrates was tested in HeLa cell extracts suggest that exonucleases rather than endonucleases are involved in the excision of U17 and U19 RNAs: (1) Cutoff products that would be expected from endonucleolytic cleavages were not detected; (2) capping or circularization of substrates inhibited formation of snoRNAs; and (3) U17 RNA was faithfully processed from a substrate carrying unrelated flanking sequences. To study in vivo processing the coding regions of snoRNAs were inserted into intron 2 of the human beta-globin gene. Expression of resulting pre-mRNAs in simian COS cells resulted in formation of correctly processed snoRNAs and of the spliced globin mRNA, demonstrating that snoRNAs can be excised from a nonhost intron and that their sequences contain all the signals essential for accurate processing. When the U17 sequence was placed in a beta-globin exon, no formation of U17 RNA took place, and when two U17 RNA-coding regions were placed in a single intron, doublet U17 RNA molecules accumulated. The results support a model according to which 5'-->3' and 3'-->5' exonucleases are involved in maturation of U17 and U19 RNAs and that excised and debranched introns are the substrates of the processing reaction.

Base Sequence↗