The human gene encoding tryptophanyl-tRNA synthetase: interferon-response elements and exon-intron organization

Frolova, Ludmila; Grigorieva, Anna Y.; Судомоина, М. А.; Kisselev, Lev L.

doi:10.1016/0378-1119(93)90568-n

Cited by 41 publications

(27 citation statements)

References 41 publications

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“…Data from prior studies have demonstrated that IFN-␥ can enhance the expression of TTS in T cells (46,50). We found that RA patient-derived SF contained high levels of inflammatory cytokines IFN-␥ and TNF-␣ that are responsible for up-regulating the expression of TTS in T cells.…”

Section: Discussionsupporting

confidence: 48%

Synovial Autoreactive T Cells in Rheumatoid Arthritis Resist IDO-Mediated Inhibition

Zhu

Wang

et al. 2006

The Journal of Immunology

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A hallmark of T cell-mediated autoimmunity is the persistence of autoreactive T cells. However, it remains to elucidate the manner in which synovial T cells are sustained in patients with rheumatoid arthritis (RA). We found that dendritic cells (DC) and tissues from the synovial joints of RA patients expressed higher levels of IDO than DC from healthy donors. Interestingly, T cells derived from the joint synovial fluid (SF) of RA patients proliferated in response to either autologous or allogeneic IDO-positive DC, an outcome that was not affected by the addition of IDO inhibitor 1-methyl-d-tryptophan (1-MT). In contrast, addition of 1-MT to the culture stimulated with allogeneic or autologous IDO-positive DC significantly enhanced the proliferation of T cells derived from peripheral blood of healthy donors or from peripheral blood of RA patients. Furthermore, we found that functionally active tryptophanyl-tRNA-synthetase (TTS) was significantly elevated in T cells derived from the SF of RA patients, leading to enhanced storage of tryptophan in T cells and to subsequent resistance to IDO-mediated deprivation of tryptophan. The RA SF enhancement of TTS expression in T cells was blocked by mAb to IFN-γ and TNF-α. These results suggest that the resistance of T cells to IDO-mediated deprivation of tryptophan represents a mechanism by which autoreactive T cells are sustained in vivo in RA patients. Specifically, blocking of the up-regulation of TTS expression in T cells presents an avenue for development of a novel therapeutic approach to treatment of RA.

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Section: Discussionsupporting

confidence: 48%

Synovial Autoreactive T Cells in Rheumatoid Arthritis Resist IDO-Mediated Inhibition

Zhu

Wang

et al. 2006

The Journal of Immunology

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“…Under apoptotic conditions secretion of aminoacyl-tRNA synthetase may contribute to this process both by arresting translation and by producing cytokines derived from their cleavage (79). The WRS-encoding gene contains IFN-response regulatory elements (80), and it has been recently suggested that the induction of WRS by IFN may play a role in safeguarding tryptophan incorporation for the IFN-enhanced synthesis of immunological molecules (81). In addition, strong induction of the WRS gene during the delayed-type hypersensitivity reaction suggests its involvement in the immune response in vivo (82).…”

Section: Signature Of Ifn-␥-induced Proteins In Aging Epidermismentioning

confidence: 99%

Protein Profiling of the Human Epidermis from the Elderly Reveals Up-regulation of a Signature of Interferon-γ-induced Polypeptides That Includes Manganese-superoxide Dismutase and the p85β Subunit of Phosphatidylinositol 3-Kinase

Gromov

Skovgaard

Pálsdóttir

et al. 2003

Molecular & Cellular Proteomics

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“…Of interest, we identified a subset of HARSL transcripts that contain an alternatively spliced exon mapping within the 5 0 -UTR. A putative set of alternatively spliced 5 0 -UTR exons has also been identified upstream of the human gene encoding TrpRS [26]. The extent and significance of these alternative-splicing events are unknown but are currently under investigation.…”

Section: Discussionmentioning

confidence: 99%

Genomic organization, transcriptional mapping, and evolutionary implications of the human bi-directional histidyl-tRNA synthetase locus (HARS/HARSL)

O’Hanlon

Miller

2002

Biochemical and Biophysical Research Communications

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Histidyl-tRNA synthetase catalyses the covalent ligation of histidine to its cognate tRNA as an early step in protein biosynthesis. In humans, the histidyl-tRNA synthetase gene (HARS) is oriented opposite of a synthetase-like gene (HARSL) that bears striking homology to HARS. In this report, we describe the genomic organization of the HARS/HARSL locus and map multiple transcripts originating from a bi-directional promoter controlling the differential expression of these genes. The HARS and HARSL genes each contain 13 exons with strong structural and sequence homology over exons 3-12. HARS transcripts originate from two distinct promoters; a cluster of short transcripts map 15-65 bp upstream of the HARS ORF while a single, longer transcript (352 bp 5 0 -UTR) maps to a distal promoter. Similarly, multiple HARSL transcripts (mapping 10-198 bp upstream of its ORF) are produced by the shared bi-directional promoter. Human and rodent HARS/HARSL loci are homologous and support a model of inverted gene duplication to explain the emergence of HARSL during mammalian evolution. Ó

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The human gene encoding tryptophanyl-tRNA synthetase: interferon-response elements and exon-intron organization

Cited by 41 publications

References 41 publications

Synovial Autoreactive T Cells in Rheumatoid Arthritis Resist IDO-Mediated Inhibition

Synovial Autoreactive T Cells in Rheumatoid Arthritis Resist IDO-Mediated Inhibition

Protein Profiling of the Human Epidermis from the Elderly Reveals Up-regulation of a Signature of Interferon-γ-induced Polypeptides That Includes Manganese-superoxide Dismutase and the p85β Subunit of Phosphatidylinositol 3-Kinase

Genomic organization, transcriptional mapping, and evolutionary implications of the human bi-directional histidyl-tRNA synthetase locus (HARS/HARSL)

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