SEARCH · Search PubMed

Results for “tRNA modification”

Search indexed PubMed citations on genomics, clinical trials, systematic reviews and public health. Explore titles, authors and supplied subject terms, then open the PubMed record.

SourceResearch connectionFrom yearThrough year

Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.

1,448 records · Page 81Linked to original sources

PubMed2006

Evidence for an early gene duplication event in the evolution of the mitochondrial transcription factor B family and maintenance of rRNA methyltransferase activity in human mtTFB1 and mtTFB2.

Most metazoans have two nuclear genes encoding orthologues of the well-characterized Saccharomyces cerevisiae mitochondrial transcription factor B (sc-mtTFB). This class of transcription factors is homologous to the bacterial KsgA family of rRNA methyltransferases, which in Escherichia coli dimethylates adjacent adenine residues in a stem-loop of the 16S rRNA. This posttranscriptional modification is conserved in most metazoan cytoplasmic and mitochondrial rRNAs. Homo sapiens mitochondrial transcription factor B1 (h-mtTFB1) possesses this enzymatic activity, implicating it as a dual-function protein involved in mitochondrial transcription and translation. Here we demonstrate that h-mtTFB2 also has rRNA methyltransferase activity but is a less efficient enzyme than h-mtTFB1. In contrast, sc-mtTFB has no detectable rRNA methyltransferase activity, correlating with the lack of the corresponding modification in the mitochondrial rRNA of budding yeast. Based on these results, and reports that Drosophila melanogaster mtTFB1 and mtTFB2 do not have completely overlapping functions, we propose a model for human mtDNA regulation that takes into account h-mtTFB1 and h-mtTFB2 likely having partially redundant transcription factor and rRNA methyltransferase functions. Finally, phylogenetic analyses of this family of proteins strongly suggest that the presence of two mtTFB homologues in metazoans is the result of a gene duplication event that occurred early in eukaryotic evolution prior to the divergence of fungi and metazoans. This model suggests that, after the gene duplication event, differential selective pressures on the rRNA methyltransferase and transcription factor activities of mtTFB genes occurred, with extreme cases culminating in the loss of one of the paralogous genes in certain species.

Animals↗

PubMed2006

Identification and characterization of RsmE, the founding member of a new RNA base methyltransferase family.

A variety of RNA methyltransferases act during ribosomal RNA maturation to modify nucleotides in a site-specific manner. However, of the 10 base-methylated nucleotides present in the small ribosomal subunit of Escherichia coli, only three enzymes responsible for modification of four bases are known. Here, we show that the protein encoded by yggJ, a member of the uncharacterized DUF558 protein family of predicted alpha/beta (trefoil) knot methyltransferases is responsible for methylation at U1498 in 16S rRNA. The gene is well-conserved across bacteria and plants, and likely performs the same function in other organisms. A yggJ deletion strain lacks the methyl group at U1498 as well as the specific methyltransferase activity. Moreover, purified recombinant YggJ specifically methylates m3U1498 in vitro. The deletion strain was unaffected in exponential growth in rich or minimal media at multiple temperatures, but it was defective when grown in competition with isogenic wild-type cells. Based on these data, we conclude that yggJ is the founding member of a family of RNA base methyltransferases, and propose that it be renamed rsmE.

Amino Acid Sequence↗

PubMed1975

Inhibitors of protein synthesis. 4. Studies on the structure-activity relationship of gougerotin and some of its analogs.

Seventeen structural analogs of gougerotin have been compared with the parent compound as inhibitors of the growh of E. coli B and as inhibitors of N-acetylphenylalanylpuromycin formation. The analogs comprise compounds with (1) an intact sarcosyl-D-seryl moiety and modifications at various positions of the carbohydrate moiety, (2) compounds which lack the peptidyl residue, and (3) compounds in which the sarcosyl-D-seryl moiety has been replaced by other aminoacyl or peptidyl moieties and in which various sites in the carbohydrate moiety have been modified in addition. These comparisons revealed that (1) the 3'-hydroxyl group makes a strong contribution to inhibitory activity, (2) the introduction of a double bond between the 2' and 3' positions of the carbohydrate moiety causes a marked decrease in activity; however, if in addition the sarcosyl-D-seryl moiety is replaced by the epsilon-N-methyl-beta-L-arginyl side chain, full activity is restored, (3) there is a marked degree of stereospecificity around the alpha carbon of the seryl moiety (replacement of the sarcosyl-D-seryl residue with the sarcosyl-L-seryl residue results in greatly reduced activity), and (4) replacement of the carboxamide group at position 5' with a hydroxymethyl function resulsts in reduced activity which is further decreased by alterations in the sarcosyl-D-seryl moiety. These alterations include (a) replacement of the D-seryl residue of the sarcosyl-D-seryl moiety by the D-alanyl or the D-phenylalanyl residues and (b) replacement of the whole sarcosyl-D-seryl side chain by the D-seryl, D-alanyl, D-phenylalanyl, p-methoxy-D-phenylalanyl, or p-methoxy-L-phenylalanyl moieties; the replacement of the sarcosyl-D-seryl side chain with the various aminoacyl residues did not lead to acceptor (puromycin-like) activity with N-Ac-Phe-tRNA as the donor.

Aminoglycosides↗

PubMed2003

Inhibition of transfer messenger RNA aminoacylation and trans-translation by aminoglycoside antibiotics.

Transfer messenger RNA (tmRNA) directs the modification of proteins of which the biosynthesis has stalled or has been interrupted. Here, we report that aminoglycosides can interfere with this quality control system in bacteria, termed trans-translation. Neomycin B is the strongest inhibitor of tmRNA aminoacylation with alanine (K(i) value of approximately 35 micro m), an essential step during trans-translation. The binding sites of neomycin B do not overlap with the identity determinants for alanylation, but the aminoglycoside perturbs the conformation of the acceptor stem that contains the aminoacylation signals. Aminoglycosides reduce the conformational freedom of the transfer RNA-like domain of tmRNA. Additional contacts between aminoglycosides and tmRNA are within the tag reading frame, probably also disturbing reprogramming of the stalled ribosomes prior protein tagging. Aminoglycosides impair tmRNA aminoacylation in the presence of all of the transfer RNAs from Escherichia coli, small protein B, and elongation factor Tu, but when both proteins are present, the inhibition constant is 1 order of magnitude higher. SmpB and elongation factor Tu have RNA chaperone activities, ensuring that tmRNA adopts an optimal conformation during aminoacylation.

Acylation↗

PubMed2006

Regulation of imprinted DNA methylation.

DNA methylation is an essential enzymatic modification in mammals. This common epigenetic mark occurs predominantly at the fifth carbon of cytosines within the palindromic dinucleotide 5'-CpG-3'. The majority of methylated CpGs are located within repetitive elements including centromeric repeats, satellite sequences and gene repeats encoding ribosomal RNAs. CpG islands, frequently located at the 5' end of genes, are typically unmethylated. DNA methylation also occurs at imprinted genes which exhibit parent-of-origin-specific patterns of methylation and expression. Imprinted methylation at differentially methylated domains (DMDs) is one of the regulatory mechanisms controlling the allele-specific expression of imprinted genes. Proper control of DNA methylation is needed for normal development and loss of methylation control can contribute to initiation and progression of tumorigenesis (reviewed in Plass and Soloway, 2002). Because patterns of imprinted DNA methylation are highly reproducible, imprinted loci make useful models for studying regulation of DNA methylation and may provide insights into how this regulation goes awry in cancer. Here, we review what is currently known about the mechanisms regulating imprinted DNA methylation. We will focus on cis-acting DNA sequences, trans-acting protein factors and the possible involvement of RNAs in control of imprinted DNA methylation.

Animals↗

PubMed2002

Cloning and expression of PARP-3 (Adprt3) and U3-55k, two genes closely linked on mouse chromosome 9.

Post-translational modification of nuclear proteins by poly(ADP-ribose) polymerase 1 (PARP-1) is involved in the regulation of DNA repair, cell death, and maintenance of genomic stability. Recently, several PARP-1 homologues have been identified constituting a family of poly(ADP-ribosyl)ating proteins. We cloned and sequenced the cDNAs of the mouse PARP-3 (Adprt3) gene encoding poly(ADP-ribose) polymerase 3 and of the closely linked U3-55k gene coding for the U3 small nucleolar ribonucleoprotein complex-associated 55-kilodalton protein. The two genes are located in a head-to-head orientation on mouse chromosome 9 and are linked by an approximately 1.5-kb putative bi-directional promoter region. This gene arrangement is conserved between mouse and human orthologues. Three alternative non-coding 5'-end exons were found in the mouse PARP-3 mRNA. The expression patterns of PARP-3, U3-55k, PARP-2, and PARP-1 genes were determined using Northern blot with mRNA from various adult mouse tissues and organs. PARP-3 expression was found to be regulated in a tissue-specific manner. The highest expression of PARP-3 was detected in the skeletal muscle, high to moderate levels were found in the lung, liver, kidney, ovary, spleen and heart, while thymus, small intestine and colon contained lower levels of the PARP-3 transcripts. Notably, PARP-3 expression was barely detectable in the whole brain and testis mRNA. In contrast to PARP-3, the other three genes showed ubiquitous expression with less variable mRNA levels. Interestingly, the mouse and human PARP-2 gene has recently been shown to be connected via a bi-directional promoter with the gene for the RNase P RNA subunit (Amé et al., J. Biol. Chem. 276: 11092-11099, 2001). As both the U3-55k protein and the RNase P RNA are involved in the processing of precursor RNAs of the protein-synthesizing machinery (pre-rRNA and pre-tRNA, respectively), it is tempting to hypothesize that expression of some members of the two groups of genes (i.e. PARP vs. protein-synthesizing machinery RNA-processing genes) may be coordinately regulated under certain physiological or pathological conditions and/or in some cell types.

Alternative Splicing↗

PubMed1978

HeLa cell RNA (2'-O-methyladenosine-N6-)-methyltransferase specific for the capped 5'-end of messenger RNA.

A novel enzyme involved in the post-transcriptional modification of the 5'-end of mRNA has been partially purified from HeLa cells. Termed an S-adenosyl-L-methionine:RNA(2'-O-methyladenosine-N4)-methyltransferase, the enzyme specifically catalyzes the transfer of a methyl group from S-adenosylmethionine to the N6 position of a 2'-O-methyladenosine residue located within the "capped" 5'-end of mRNA. The dimethylated nucleoside, N6,2'-O-dimethyladenosine, is formed as indicated by the following reaction in which m7G(5')pppAm- represents the capped and methylated 5'-end of mRNA: AdoMet + m7G(5')pppAm- leads to AdoHcy + m7G(5')pppm6A7- Greatest activity is obtained with RNA acceptors ending in m7G(5')pppAm-; less activity is found with RNA ending in m7G(5')pppA-; and barely detectable and no activity is found with RNA ending in G(5')pppA- and ppA-, respectively. Furthermore, no activity is found with oligonucleotides such as m7G(5')pppA, m7G(5')pppAm, and m7G(5')pppAmpN indicating that a longer polymer is required. It can be concluded from the substrate specificity of the enzyme that the formation of N6,2'-O-dimethyladenosine follows the biosynthesis of molecules containing m7G(5')pppAm-N-. The molecular weight of the methyltransferase, as determined by sedimentation in sucrose gradients, is approximately 65,000.

Adenosine↗

PubMed2002

Complexities in ETS-domain transcription factor function and regulation: lessons from the TCF (ternary complex factor) subfamily. The Colworth Medal Lecture.

The ETS-domain transcription factor family can be divided into a series of subfamilies. Elk-1 represents the founding member of the ternary complex factor (TCF) subfamily. By focusing on the TCF subfamily, we can demonstrate the complexities that exist in the function and regulation of ETS-domain transcription factors. This article focuses on Elk-1 in detail and summarizes the functions of other TCFs. The key themes covered include the domain structure of the TCFs, the mechanisms of complex formation with serum response factor, regulation of TCFs by mitogen-activated protein kinase cascades, and transcriptional regulatory properties of the TCFs. Finally, the emerging role of the TCFs in vivo is discussed. A picture is developing indicating that, while these proteins exhibit significant sequence and functional conservation, key differences in their structure and regulation are being identified which may relate to unique functions of these proteins in vivo.

Amino Acid Sequence↗