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PubMed2001

Death of motoneurons induced by trophic deprivation or by excitotoxicity is not prevented by overexpression of SMN.

The telomeric copy of the survival motor neuron gene (SMN1) is deleted or mutated in all spinal muscular atrophy (SMA) patients and these patients present mainly a loss in spinal motoneurons. Although studies performed in HeLa cells suggest that SMN may be involved in the biogenesis and possibly in recycling of spliceosomal small nuclear ribonucleoproteins (snRNPs), no link has been established between this function and the consequence of the absence of SMN in the specific loss of motoneurons. We attempted to answer the question of whether SMN plays a direct role in motoneuron survival by transducing cultured motoneurons with lentiviral vectors coding either for an antisense Smn mRNA or for full-length or truncated forms of SMN. We studied their effect on survival under different anti- or proapoptotic culture conditions. Our results show that increased levels of SMN are unable to protect motoneurons from death induced by trophic deprivation or by excitotoxicity. These results suggest that SMN is not a survival factor per se for motoneurons. In addition, overexpression of a truncated form of SMN shown to induce a modified subcellular localization and to exert a dominant-negative effect on snRNP biogenesis and RNA splicing in HeLa cells was ineffective in modifying both localization and survival in motoneurons.

Animals↗
PubMed1995

Analysis of 43 kb of the Chlorella virus PBCV-1 330-kb genome: map positions 45 to 88.

Forty-three kb of DNA, located at the left end (45 to 88 kb) of the 330-kb Chlorella virus PBCV-1 genome, was sequenced and analyzed. Eighty-six open reading frames (ORFs) 65 codons or longer were identified; 47 were classified as major ORFs. These 47 major ORFs are densely packed on both strands of PBCV-1 DNA. Seventeen of these major ORFs resemble genes in the sequence databases, including three putative gene products involved in manipulating sugars (glucosamine synthetase, GDP-D-mannose dehydratase, and N-acetylglucosaminyltransferase), two transcription factors, beta-1,3-glucanase, aspartate transcarbamylase, ubiquitin carboxy terminal hydrolase, RNA guanyl transferase, an exonuclease, and a helicase. This is the first time some of these putative PBCV-1 genes have been found in a virus genome. One of the transcription factor-like genes contains a type IB self-splicing intron. Since a spliceosomal processed intron was reported previously in the PBCV-1 DNA polymerase gene, PBCV-1 is the first virus known to contain two different types of introns.

Amino Acid Sequence↗
PubMed2001

Intron conservation in the DNA polymerase gene encoded by Chlorella viruses.

Previously we reported that 19 of 42 viruses that infect Chlorella strain NC64A (NC64A viruses) contain a short, nuclear-located, spliceosomal-processed intron in a pyrimidine dimer-specific glycosylase/apyrimidine lyase (pdg) gene. Surprisingly, the nucleotide sequence of the intron region is more conserved than the exon regions of the gene (L. Sun et al., 2000, J. Mol. Evol. 50, 82-92). For comparative purposes, we determined the nucleotide sequence of a similar intron type and its flanking coding regions in the DNA polymerase (dnapol) gene from the same 42 NC64A viruses and also 5 viruses that infect Chlorella strain Pbi. Thirty-eight of the 42 NC64A viruses contained a 101-nucleotide intron and the remaining 4 had an 86-nucleotide intron located in the same position in dnapol. The 4 viruses with the smaller intron in dnapol also have a smaller intron in their pdg gene. There was no intron in the dnapol gene of the 5 Pbi viruses. Phylogenetic analyses indicate that the dnapol genes containing the 86-nucleotide intron represent the ancestral condition among the NC64A viruses. The intron in the dnapol gene is phase 0 (keeps codons intact), which differs from the phase 1 intron in the pdg gene. The intron in the dnapol gene, unlike the pdg intron, was conserved (83 to 100% identical) to about the same extent as the coding regions of the gene (78 to 100% identical).

Amino Acid Sequence↗
PubMed2000

Regulation of neuronal cell death and differentiation by NGF and IAP family members.

Nerve growth factor (NGF) and other neurotrophins were identified because of their trophic role for distinct populations of neurons in the peripheral nervous system. We know that neuronal cell death is regulated by a genetically encoded programme, called apoptosis, that is conserved from worms to humans. Dysregulation of this programme is thought to contribute to neurodegenerative diseases which are characterized by the loss of neurons. This article will review recent findings about the motoneuron disease spinal muscular atrophy (SMA). Two closely linked candidate genes for SMA, the SMN (survival motor neuron) gene and the NAIP (neuronal apoptosis inhibitory protein) gene have been reported. The SMN protein forms a complex with several other proteins and this complex containing SMN plays a critical role in the assembly of spliceosomes and in pre-mRNA splicing. NAIP, c-IAP1 (inhibitor of apoptosis-1), c-IAP2, X-IAP and survivin comprise the mammalian inhibitor of apoptosis family. Its members can protect mammalian cells from apoptosis induced by a variety of stimuli. Some of the IAP molecules have been shown to interact both with cell signalling molecules and with specific caspases but details concerning their cellular role are only incompletely characterized.

Animals↗
PubMed1995

The marine red alga Chondrus crispus has a highly divergent beta-tubulin gene with a characteristic 5' intron: functional and evolutionary implications.

We characterized a nuclear gene and its corresponding cDNA encoding beta-tubulin (gene TubB1) of the marine red alga Chondrus crispus. The deduced TubB1 protein is the most divergent beta-tubulin so far reported with only 64 to 69% amino acid identity relative to other beta-tubulins from higher and lower eukaryotes. Our analysis reveals that TubB1 has an accelerated evolutionary rate probably due to a release of functional constraints in connexion with a specialization of microtubular structures in rhodophytes. It further indicates that isoform diversity and functional differentiation of tubulins in eukaryotic cells may be controlled by independent selective constraints. TubB1 has a short spliceosomal intron at its 5' end which seems to be a characteristic feature of nuclear protein-coding genes from rhodophytes. The splice junctions of the four known rhodophyte introns comply well with the corresponding consensus sequences of higher plants in agreement with previous suggestions from phylogenetic inference that red algae and green plants may be sister groups. The paucity and asymmetrical location of introns in rhodophyte genes can be explained by differential intron loss due to conversion of genes by homologous recombination with cDNAs corresponding to reverse transcribed mRNAs or partially spliced pre-mRNAs, respectively. The identification of an intron containing TubB1 cDNA in C. crispus confirms that pre-mRNAs can escape both splicing and degradation in the nucleus prior to transport into the cytoplasm. Differential Southern hybridizations under non-stringent conditions with homologous and heterologous probes suggest that C. crispus contains a second degenerate beta-tubulin gene (or pseudogene?) which, however, is only distantly related to TubB1 as it is to the more conserved homologues of other organisms.

Amino Acid Sequence↗
PubMed1995

Characterization of the nuclear gene encoding mitochondrial aconitase in the marine red alga Gracilaria verrucosa.

We have cloned a nuclear gene from the marine red alga Gracilaria verrucosa that encodes the complete 779 amino-acid mitochondrial aconitase (m-ACN), the first characterized from a photosynthetic organism. The N-terminal 28 deduced amino acids are predicted to constitute the mitochondrial transit peptide, the first described from a red alga. Putative transcriptional cis-acting elements were identified in the upstream untranslated region. The G. verrucosa m-ACN gene (m-ACN) is present in a single copy and is located ca. 1.5 kb upstream from the single-copy polyubiquitin gene. The single spliceosomal intron is located near the 5' end of the region encoding the mature m-ACN in precisely the same location and phase as intron 2 in Caenorhabditis elegans m-ACN; sequences at its 3' and 5' splice junctions and at the predicted lariat branch point conform well to the eukaryote consensus sequences. Multiple protein-sequence alignment of m-ACN, bacterial aconitase (b-ACN) and iron-responsive element-binding protein (IRE-BP), and phylogenetic analyses, revealed that m-ACN does not share a recent common ancestry with either b-ACN or IRE-BP.

Aconitate Hydratase↗
PubMed1991

U1 SnRNP association with HnRNP involves an initial non-specific splice-site independent interaction of U1 SnRNP protein with HnRNA.

Precursor mRNA is complexed with proteins in the cell nucleus to form heterogeneous nuclear ribonucleoprotein (hnRNP), and these hnRNPs are found associated in vivo with small nuclear RNPs (snRNPs) for the processing of pre-mRNA. In order to better characterize the ATP-independent initial association of U1 snRNP with hnRNP, an important early event in assembly of the spliceosome complex, we have determined some of the components essential to an in vitro reassociation of U1 snRNP with hnRNP. U1 snRNP reassociated in vitro with 40S hnRNP particles from HeLa cells and, similar to the in vivo hnRNP/U1 snRNP association, the in vitro interaction was sensitive to high salt concentrations. U1 snRNP also associated with in vitro reconstituted hnRNP in which bacteriophage MS2 RNA, which lacks introns, was used as the RNA component. Purified snRNA alone would not associate with the MS2 RNA-reconstituted hnRNP, however, intact U1 snRNP did interact with protein-free MS2 RNA. This indicates that the U1 snRNP proteins are required for the hnRNP/U1 snRNP association, but hnRNP proteins are not. Thus, the initial, ATP-independent association of U1 snRNP with hnRNP seems to be mediated by U1 snRNP protein(s) associating with hnRNA without requiring a splice-site sequence. This complex may then be further stabilized by intron-specific interactions and hnRNP proteins, as well as by other snRNPs.

Base Sequence↗
PubMed1991

Genetic studies of the PRP11 gene of Saccharomyces cerevisiae.

PRP11 is a gene that encodes an essential function for pre-messenger RNA (mRNA) processing in Saccharomyces cerevisiae. We have carried out a mutational study to locate essential and non-essential regions of the PRP11 protein. The existing temperature-sensitive (ts) mutation (prp11-1) was isolated from the chromosome of the original mutant and its position in the gene was determined. When the prp11-1 gene was transcribed from the GAL1 promoter, the overproduced protein was able to reverse the ts prp11-1 phenotype; this is compatible with the possibility that the defect in the prp11-1 gene product affects its binding to the spliceosome. Thirteen linker-insertion mutations were constructed. Only five (prp11-4, 11-6, 11-10, -13 and -14) resulted in a null phenotype. One of these became temperature-sensitive when the insertion was reduced in size from four (prp11-10) to two (prp11-15) amino acids. A sequence of ten amino acids of which also occurs in the human U1 small nuclear ribonucleoprotein particle (snRNP) A protein and the U2 snRNP B" protein, when deleted from PRP11, had no phenotype and thus appears to be nonessential for PRP11 function. However, a linker-insertion mutation (prp11-10) immediately adjacent to this region resulted in a null phenotype.

Amino Acid Sequence↗
PubMed1995

Rescue of the fission yeast snRNA synthesis mutant snm1 by overexpression of the double-strand-specific Pac1 ribonuclease.

The Schizosaccharomyces pombe temperature-sensitive mutant snm1 maintains reduced steady-state quantities of the spliceosomal small nuclear RNAs (snRNAs) and the RNA subunit of the tRNA processing enzyme RNase P. We report here the isolation of the pac1+ gene as a multi-copy suppressor of snm1. The pac1+ gene was previously identified as a suppressor of the ran1 mutant and by its ability to cause sterility when overexpressed. The pac1+ gene encodes a double-strand-specific ribonuclease that is similar to RNase III, an RNA processing and turnover enzyme in Escherichia coli. To investigate the essential structural features of the Pac1 RNase, we altered the pac1+ gene by deletion and point mutation and tested the mutant constructs for their ability to complement the snm1 and ran1 mutants and to cause sterility. These experiments identified four essential amino acids in the Pac1 sequence: glycine 178, glutamic acid 251, and valines 346 and 347. These amino acids are conserved in all RNase III-like proteins. The glycine and glutamic acid residues were previously identified as essential for E. coli RNase III activity. The valines are conserved in an element found in a family of double-stranded RNA binding proteins. Our results support the hypothesis that the Pac1 RNase is an RNase III homolog and suggest a role for the Pac1 RNase in snRNA metabolism.

Amino Acid Sequence↗
PubMed1994

Cloning and characterization of the nuclear gene encoding plastid glyceraldehyde-3-phosphate dehydrogenase from the marine red alga Gracilaria verrucosa.

The single-copy nuclear gene (GapA), encoding the plastid-localized glyceraldehyde-3-phosphate dehydrogenase (GAPDH) of the marine red alga Gracilaria verrucosa, has been cloned and sequenced. The GapA transcriptional initiation site was located 49 bp upstream of the start codon, and a putative TATA box was found 54 bp farther upstream. A spliceosomal intron was identified in the transit-peptide-encoding region in a position very similar to intron 1 of GapA and GapB of higher plants; no introns occur in the region encoding the mature protein. These observations provisionally suggest that both red algae and higher plants descend from a single ancestral photosynthetic eukaryote, i.e. that a single endosymbiotic event gave rise to red algal and higher-plant plastids.

Amino Acid Sequence↗
PubMed1995

The nuclear gene and cDNAs encoding cytosolic glyceraldehyde-3-phosphate dehydrogenase from the marine red alga Gracilaria verrucosa: cloning, characterization and phylogenetic analysis.

We have cloned and sequenced the single-copy nuclear gene (GapC) encoding the complete 335-amino acid cytosolic glyceraldehyde-3-phosphate dehydrogenase (GAPC) from the red alga Gracilaria verrucosa. The proline residue which contributes to the specificity of NAD+ binding in other GAPC-like proteins is present. Putative regulatory regions, including GC-rich regions, a GATA element, and 11-base T- and T/G-clusters, but excluding TATA- and CCAAT-boxes, were identified upstream. Two types of GapC cDNAs differing in polyadenylation site were characterized. An 80-bp phase-two spliceosomal intron was identified in a novel position interrupting the highly conserved cofactor-coding region I. The G. verrucosa GAPC was easily aligned with other known GAPC-type sequences. Inferred phylogenetic trees place red algae among the eukaryote crown taxa, although with modest bootstrap support and without stable resolution among related GAPC lineages.

Amino Acid Sequence↗
PubMed1994

Changes in UsnRNA biosynthesis during rat liver regeneration.

Partial hepatectomy (P.H.) induces a partially synchronized growth response of liver under normal regulation of growth. In this phase changes in cellular morphology, radial distribution pattern of cells and other biological as well as major biochemical changes are well documented. Here, we have shown that the cellular content of UsnRNAs altered during this proliferative phase as well. The level of spliceosomal UsnRNAs (U1, U2, U4-U6) gradually decreased by 30-50% upto 48 hrs of P.H. followed by gradual increase to reach the normal level within one month of P.H. The U3 snRNA level on the other hand, was nearly equal to that in normal liver at 48 hrs of P.H. but in 24 and 72 hrs of P.H. its level was high (4 fold) in contrast to that in other UsnRNAs. Thus, it is clear from our data that the level of all the six UsnRNAs decreased during 48 hrs of P.H. compared to that after first 24 hrs. This has been correlated in the kinetics of UsnRNAs' synthesis (in terms of labelling) in isolated hepatocytes, where the rate of labelling of all the six UsnRNAs increased 20-30% in 24 hrs regenerating hepatocytes (R.H.) followed by sharp decrease by 30-50% within next 24 hrs, compared to that in the normal hepatocytes. But from 72 hrs onwards in R.H. the rate of labelling of all the six UsnRNAs again increased by 30-50% (compared to that in normal hepatocytes) followed by decrease of their labelling-rate to reach the normal level in R.H. within one month of P.H.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1994

A histochemical approach to the knowledge about the neuron nucleus: the "pre-alarm chromatin".

Chromatin as a functional whole. Since the nineteen-fifties (1,2), studies on the histochemistry of the nucleus have been based on its concept as a whole: measurement of the DNA content, and the ratio between nucleus size and cell size appeared to be (and were in effect) an indication of the functional status of the single cell and of the cell population. Two decades later, the already well-known morphological distinction between the chromatins as euchromatin and heterochromatin was reinterpreted on the basis of the degree of spiralization of the nucleosomal fiber and its complexity (3). Subsequently, considerable information about the non-random interphasic position of the chromosomal domains in the nucleus was obtained by in situ hybridization, and the successive reconstruction of their location in the nucleus by image processing with Normarski optics and rotating stage or by confocal microscopy (4-8). Moreover, immunological studies using monoclonal antibodies raised against the splicing factors acting on nuclear pre-mRNAs in discrete nuclear regions (spliceosomes) (9,10), lent support to the notion that the chromatin machinery operates as a whole.

Animals↗
PubMed1994

Changes in UsnRNA biosynthesis during rat liver regeneration.

Partial hepatectomy (P.H.) induces a partially synchronized growth response of liver under normal regulation of growth. In this phase changes in cellular morphology, radial distribution pattern of cells and other biological as well as major biochemical changes are well documented [24]. Here, we have shown that the cellular content of UsnRNAs altered during this proliferative phase as well. The level of spliceosomal UsnRNAs (U1, U2, U4-U6) gradually decreased by 30-50% upto 48 hrs of P.H. followed by gradual increase to reach the normal level within one month of P.H. The U3 snRNA level on the other hand, was nearly equal to that in normal liver at 48 hrs of P.H. but in 24 and 72 hrs of P.H. its level was high (4 fold) in contrast to that in other UsnRNAs. Thus, it is clear from our data that the level of all the six UsnRNAs decreased during 48 hrs of P.H. compared to that after first 24 hrs. This has been correlated in the kinetics of UsnRNAs' synthesis (in terms of labelling) in isolated hepatocytes, where the rate of labelling of all the six UsnRNAs increased 20-30% in 24 hrs regenerating hepatocytes (R.H.) followed by sharp decrease by 30-50% within next 24 hrs, compared to that in the normal hepatocytes.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1997

Intron distribution in ancient paralogs supports random insertion and not random loss.

The intron positions of ten different protein families were examined to determine (the statistical likelihood of) whether spliceosomal introns are the result of random insertion events into previously intronless genes, on the one hand, or the result of random loss from common ancestral introns, on the other. The number of expected matches for the alternative scenarios was calculated for a binomial distribution by considering currently observed introns relative to all possible locations for insertion or loss. Introns occurring at approximately the same location (hereafter called a "match") were tallied for each of the paired proteins. Matches were identified by their positions in the multiple alignment and were defined as any two introns occurring within a window of 11 possible nucleotide positions, thereby allowing for possible alignment errors and "intron sliding." Matches were tallied from the raw data and compared with the expected number of matches for the two different scenarios. The results suggest that the distribution of introns in genes encoding proteins is due to random insertion and not random loss.

Animals↗
PubMed2004

Transcriptional coregulator SNW/SKIP: the concealed tie of dissimilar pathways.

Eukaryotic gene expression requires that all the steps of messenger RNA production are regulated in concert to integrate the diverse inputs cells receive. We discuss the functioning of SNW/SKIP, an essential spliceosomal component and transcriptional coregulator, which may provide regulatory coupling of transcription initiation and splicing. SNW/SKIP potentiates the activity of important transcription factors, such as vitamin D receptor, CBF1 (RBP-Jkappa), Smad2/3, and MyoD. It synergizes with Ski in overcoming pRb-mediated cell cycle arrest, and it is targeted by the viral transactivators EBNA2 and E7. SNW/SKIP may aid in conformational transition of the gene expression machine through its avidity to nuclear matrix fractions or by recruiting foldases such as the prolyl isomerase PPIL1. The extensive list of SNW/SKIP partners, its unique primary structure, conserved from yeast to humans, and its essential character suggest a distinct function of general importance.

Animals↗
PubMed1999

Small nucleolar RNAs.

Many small RNA species associate with the nucleolar structure. Some of these small nucleolar RNAs (snoRNAs) are required for cleavage processing of ribosomal RNA precursors. There are many pseudouridine residues and methylated riboses in mature ribosomal RNA. For most, if not all, of these modifications, each site is selected by base pairing with a specific snoRNA species. Some snoRNAs are needed for the 2'-O-ribose methylation of at least one spliceosomal small nuclear RNA. Many snoRNAs, particularly in yeast, are generated from independent transcription units. Most vertebrate snoRNAs are produced by processing of introns from protein-coding transcripts. Some snoRNAs are made by processing of introns from non-protein-coding transcripts.

Animals↗
PubMed2005

Actin phylogeny and intron distribution in bangiophyte red algae(rhodoplantae).

The molecular phylogeny of red algal actin genes, with emphasis on the paraphyletic "Bangiophyceae," was examined and compared to the rhodophyte SSU rDNA phylogeny. Nineteen new genomic actin sequences and seven SSU rDNA sequences were obtained and subjected to diverse phylogenetic analyses (maximum likelihood, distance/neighbor-joining, maximum parsimony, Bayesian analyses, and, with respect to protein sequences, also quartet puzzling). The actin trees confirmed most of the major clades found in the SSU rDNA phylogenies, although with a lower resolution. An actin gene duplication in the florideophycean lineage is reported, presumably related to an increased complexity of sexual reproduction. In addition, the distribution and characteristics of spliceosomal introns found in some of the actin sequences were examined. Introns were found in almost all florideophycean actin genes, whereas only two bangiophyte sequences contained introns. One intron in the florideophycean actin genes was also found in metazoan, and, shifted by one or two nucleotides, in a glaucocystophyte, a cryptophyte, and two fungal actin genes, and thus may be an ancient intron.

Actins↗