scholarly journals Gene Homologies Identified between Trypanosoma cruzi Antigen 36 and Mammalian TRIM21 Genes Using Bioinformatics Analysis

Author(s):  
Martin A Winkler ◽  
Alfred A Pan

Abstract Background We previously reported that a Human Ro52 gene sequence (TRIM21) produced a significant stretch of protein sequence homologous to T. cruzi Antigen 36 (Ag 36) protein sequence, when Ag 36 was translated in the second reading frame. Comparison of their respective DNA sequences demonstrated a 114 nucleotide region of both genes having ~ 70 percent partial homology. After Ro52 was shown to be an E3 Ubiquitin dependent Type I ligase for transcription factors for Interferon genes, we proposed that the Ag 36 gene, which contains a repetitive motif within it, may function to repress Ro52 in the human heart through RNA interference, or other unknown mechanism, giving rise to autoimmunity found in Chronic Chagas Cardiomyopathy (CCC). Results To test that hypothesis, we compared various mammalian TRIM genes to the T. cruzi Ag 36 DNA sequence using the Needleman-Wunsch algorithm in the http:\\usegalaxy.eu bioinformatics tool base. In addition to human and chimpanzee, TRIM21 comparable gene regions from canine, shrew, ferret, bat, feline, and armadillo, and aardvark showed homology to the gene for Ag 36 ranging from 68 to 30 percent. However, mouse and eight other mammalian species showed no significant homology. Since mice have been shown to have severe cardiac cardiomyopathy after infection, but their TRIM21 was not homologous to Ag 36 in this study, we conclude that the gene homology has no causative link to CCC. Conclusions In addition to human TRIM21, eight mammalian species showed partial gene homology to T. cruzi Ag 36, and some of these have been demonstrated to have CCC. However, rats and mice TRIM21 showed no partial homology to Ag 36. Since these species have been demonstrated to have CCC, the partial gene homology between Ag36 and TRIM 21 may not be causative or associated with CCC, as was originally hypothesized.

2021 ◽  
Author(s):  
Martin A Winkler ◽  
Alfred A Pan

Abstract Background: We previously reported that a Human Ro52 gene sequence (TRIM21) produced a significant stretch of protein sequence homologous to T. cruzi Antigen 36 (Ag 36) protein sequence, when Ag 36 was translated in the second reading frame. Comparison of their respective DNA sequences demonstrated a 114 nucleotide region of both genes having ~70 percent partial homology. After Ro52 was shown to be an E3 Ubiquitin dependent Type I ligase for transcription factors for Interferon genes, we proposed that the Ag 36 gene, which contains a repetitive motif within it, may function to repress Ro52 in the human heart through RNA interference, or other unknown mechanism, giving rise to autoimmunity found in Chronic Chagas Cardiomyopathy (CCC).Results: To test that hypothesis, we compared various mammalian TRIM genes to the T. cruzi Ag 36 DNA sequence using the Needleman-Wunsch algorithm in the http:\\usegalaxy.eu bioinformatics tool base. In addition to human and chimpanzee, TRIM21 comparable gene regions from canine, shrew, ferret, bat, feline, and armadillo, and aardvark showed homology to the gene for Ag 36 ranging from 68 to 30 percent. However, mouse and eight other mammalian species showed no significant homology. Since mice have been shown to have severe cardiac cardiomyopathy after infection, but their TRIM21 was not homologous to Ag 36 in this study, we conclude that the gene homology has no causative link to CCC.Conclusions: In addition to human TRIM21, eight mammalian species showed partial gene homology to T. cruzi Ag 36, and some of these have been demonstrated to have CCC. However, rats and mice TRIM21 showed no partial homology to Ag 36. Since these species have been demonstrated to have CCC, the partial gene homology between Ag36 and TRIM 21 may not be causative or associated with CCC, as was originally hypothesized.


1996 ◽  
Vol 319 (3) ◽  
pp. 749-754 ◽  
Author(s):  
Sally E PEMBLE ◽  
Anthony F WARDLE ◽  
John B TAYLOR

We have isolated a cDNA clone that encodes rat glutathione S-transferase (GST) subunit 13, a GST originally isolated from rat liver mitochondrial matrix by Harris, Meyer, Coles and Ketterer [(1991) Biochem. J. 278, 137–141]. The 896 bp cDNA contains an open reading frame of 678 bp encoding a deduced protein sequence of which the first 33 residues (excluding the initiation methionine residue) correspond to the N-terminal sequence reported by Harris et al. Hence like many other nuclear-encoded, mitochondrially located proteins, there is no cleavable mitochondrial presequence at the N-terminus. GST subunit 13 was originally placed into the Theta class of GSTs on the basis of sequence identity at the N-terminus; however, this is the only identity with the Theta class and in fact GST subunit 13 shows little sequence similarity to any of the known GST classes. Most importantly it lacks the SNAIL/TRAIL motif that has so far been a characteristic of soluble GSTs, although it does possess a second motif (FGXXXXVXXVDGXXXXXF) reported for GST-related proteins (Koonin, Mushegian, Tatusov, Altschul, Bryant, Bork and Valencia [(1994) Protein Sci. 3, 2045–2054]. Southern and Northern blot analyses of rat DNA and mRNA are consistent with GST subunit 13's being the product of a single hybridizing gene locus. Searches of EST databases identified numerous similar human DNA sequences and a single pig sequence. We have derived a human cDNA sequence from these EST sequences which shows a high nucleotide similarity (77%) to rat GST subunit 13. The largest open reading frame is identical in length with subunit 13 and yields a deduced protein sequence identity of 70%. Most unusually the 3´ non-coding nucleotide sequence identity is also 77%. We conclude that these cDNAs belong to a novel GST class hereby designated Kappa, with the rat GST subunit 13 gene designated rGSTK1 and the human gene being called hGSTK1.


2021 ◽  
Vol 22 (S3) ◽  
Author(s):  
Junyi Li ◽  
Huinian Li ◽  
Xiao Ye ◽  
Li Zhang ◽  
Qingzhe Xu ◽  
...  

Abstract Background The prediction of long non-coding RNA (lncRNA) has attracted great attention from researchers, as more and more evidence indicate that various complex human diseases are closely related to lncRNAs. In the era of bio-med big data, in addition to the prediction of lncRNAs by biological experimental methods, many computational methods based on machine learning have been proposed to make better use of the sequence resources of lncRNAs. Results We developed the lncRNA prediction method by integrating information-entropy-based features and machine learning algorithms. We calculate generalized topological entropy and generate 6 novel features for lncRNA sequences. By employing these 6 features and other features such as open reading frame, we apply supporting vector machine, XGBoost and random forest algorithms to distinguish human lncRNAs. We compare our method with the one which has more K-mer features and results show that our method has higher area under the curve up to 99.7905%. Conclusions We develop an accurate and efficient method which has novel information entropy features to analyze and classify lncRNAs. Our method is also extendable for research on the other functional elements in DNA sequences.


1990 ◽  
Vol 265 (22) ◽  
pp. 13351-13356
Author(s):  
S Boast ◽  
M W Su ◽  
F Ramirez ◽  
M Sanchez ◽  
E V Avvedimento

2009 ◽  
Vol 83 (10) ◽  
pp. 5056-5066 ◽  
Author(s):  
Sabine A. Bisson ◽  
Anne-Laure Page ◽  
Don Ganem

ABSTRACT Type I interferons (IFNs) are important mediators of innate antiviral defense and function by activating a signaling pathway through their cognate type I receptor (IFNAR). Here we report that lytic replication of Kaposi's sarcoma-associated herpesvirus (KSHV) efficiently blocks type I IFN signaling and that an important effector of this blockade is the viral protein RIF, the product of open reading frame 10. RIF blocks IFN signaling by formation of inhibitory complexes that contain IFNAR subunits, the Janus kinases Jak1 and Tyk2, and the STAT2 transcription factor. Activation of both Tyk2 and Jak1 is inhibited, and abnormal recruitment of STAT2 to IFNAR1 occurs despite the decrement in Tyk2 activity. As a result of these actions, phosphorylation of both STAT2 and STAT1 is impaired, with subsequent failure of ISGF3 accumulation in the nucleus. The presence in the viral genome of potent inhibitors of type I IFN signaling, along with several viral genes that block IFN induction, highlights the importance of the IFN pathway in the control of this human tumor virus infection.


2015 ◽  
Vol 113 (5) ◽  
pp. 1191-1196 ◽  
Author(s):  
Laëtitia Gorisse ◽  
Christine Pietrement ◽  
Vincent Vuiblet ◽  
Christian E. H. Schmelzer ◽  
Martin Köhler ◽  
...  

Aging is a progressive process determined by genetic and acquired factors. Among the latter are the chemical reactions referred to as nonenzymatic posttranslational modifications (NEPTMs), such as glycoxidation, which are responsible for protein molecular aging. Carbamylation is a more recently described NEPTM that is caused by the nonenzymatic binding of isocyanate derived from urea dissociation or myeloperoxidase-mediated catabolism of thiocyanate to free amino groups of proteins. This modification is considered an adverse reaction, because it induces alterations of protein and cell properties. It has been shown that carbamylated proteins increase in plasma and tissues during chronic kidney disease and are associated with deleterious clinical outcomes, but nothing is known to date about tissue protein carbamylation during aging. To address this issue, we evaluated homocitrulline rate, the most characteristic carbamylation-derived product (CDP), over time in skin of mammalian species with different life expectancies. Our results show that carbamylation occurs throughout the whole lifespan and leads to tissue accumulation of carbamylated proteins. Because of their remarkably long half-life, matrix proteins, like type I collagen and elastin, are preferential targets. Interestingly, the accumulation rate of CDPs is inversely correlated with longevity, suggesting the occurrence of still unidentified protective mechanisms. In addition, homocitrulline accumulates more intensely than carboxymethyl-lysine, one of the major advanced glycation end products, suggesting the prominent role of carbamylation over glycoxidation reactions in age-related tissue alterations. Thus, protein carbamylation may be considered a hallmark of aging in mammalian species that may significantly contribute in the structural and functional tissue damages encountered during aging.


2001 ◽  
Vol 75 (22) ◽  
pp. 11218-11221 ◽  
Author(s):  
Brendan N. Lilley ◽  
Hidde L. Ploegh ◽  
Rebecca S. Tirabassi

ABSTRACT Several herpesviruses encode Fc receptors that may play a role in preventing antibody-mediated clearance of the virus in vivo. Human cytomegalovirus (HCMV) induces an Fc-binding activity in cells upon infection, but the gene that encodes this Fc-binding protein has not been identified. Here, we demonstrate that the HCMV AD169 open reading frame TRL11 and its identical copy, IRL11, encode a type I membrane glycoprotein that possesses IgG Fc-binding capabilities.


1996 ◽  
Vol 12 (18) ◽  
pp. 1717-1724 ◽  
Author(s):  
EDUARDO N. ESTEBAN ◽  
MICHAEL P. SHERMAN ◽  
BERNARD L. POIESZ ◽  
ROBERT R. MARSHAK ◽  
DAVID J. WATERS ◽  
...  

1986 ◽  
Vol 6 (11) ◽  
pp. 3626-3631
Author(s):  
N P Shah ◽  
W Wachsman ◽  
A J Cann ◽  
L Souza ◽  
D J Slamon ◽  
...  

The mechanism of cellular transformation by the human T-cell leukemia viruses (HTLVs) is thought to involve a novel retrovirus gene known as chi. The chi gene is essential for HTLV replication and acts by enhancing transcription from the viral long terminal repeat. By using the HTLV type I and II chi gene-coding regions inserted into a highly efficient expression vector, we directly compared the efficiencies of the two chi proteins to trans activate the HTLV type I and II long terminal repeats. We demonstrate that the two chi proteins have different patterns of trans activation. The patterns were highly reproducible in all mammalian cells tested. A different pattern of activation was observed in avian cells. These results suggest that the mechanism of trans activation involves specific cellular factors that are highly conserved throughout mammalian species but different in avian cells. Understanding the mechanism of trans activation by the chi gene product may provide insights into mechanisms of cellular transformation by HTLV.


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