Regulated Capture by Exosomes of mRNAs for Cytoplasmic tRNA Synthetases

Wang, Feng; Xu, Zhiwen; Zhou, Jie; Lo, Woo-Kuen; Lau, Ching; Nangle, Leslie A.; Yang, Xiang‐Lei; Zhang, Mingjie; Schimmel, Paul

doi:10.1074/jbc.c113.490599

Cited by 21 publications

(18 citation statements)

References 31 publications

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“…Several papers describe distinctive mRNA transcriptomes in saliva from patients with breast cancer [111]; pancreatic cancer [112] and ovarian cancer [113], as compared to controls. mRNA encoding for a tRNA synthetase unique splice variant has also been shown to be released in EVs from prostate cancer cells in culture [114], but this has yet to be evaluated in urine from these patients. In addition, microarray analysis of mRNAs in serum EVs from glioblastoma patients and controls can correctly separate these two groups by unsupervised clustering analysis, although in this case the critical differences in mRNA levels seem to reflect the response of the patient cells to the tumor rather than being mRNAs in tumor-derived EVs [43]; albeit abnormally high levels of the tenascin C mRNA characteristic of glioblastoma tumors was found in serum EVs from these patients [43].…”

Section: Exrna As Biomarkers For Cancermentioning

confidence: 99%

Extracellular RNA mediates and marks cancer progression

Redzic

Balaj

Vos

et al. 2014

Seminars in Cancer Biology

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Different types of RNAs identified thus far represent a diverse group of macromolecules that are involved in the regulation of different biological processes. RNA is generally thought to be localized primarily in the nucleus and cytoplasm, however, some types of RNA have been detected in the extracellular milieu. These extracellular RNA (exRNA) molecules are protected from degradation and it is now widely accepted that extracellular vesicles and ribonucleoprotein particles serve as transport vehicles for exRNA among cells. The functional consequence of this transfer of genetic information probably encompasses a broad range of normal developmental and physiologic processes in many organisms. This review will focus on the role of exRNA communication in cancer. We will focus on different types of RNA species identified and characterized within tumor-derived extracellular vesicles. Further, we will describe the role of exRNAs in cancer progression, as well as their potential for use as diagnostic biomarkers and therapeutic tools for monitoring and treating cancer, respectively.

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Section: Exrna As Biomarkers For Cancermentioning

confidence: 99%

Extracellular RNA mediates and marks cancer progression

Redzic

Balaj

Vos

et al. 2014

Seminars in Cancer Biology

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“…Quantitative PCR and Data Analysis-Quantitative PCRs (qPCRs) were performed as described previously (9,11). The qPCR primer sequences were as follows: qFP1, CACGGTGCA-GAAGTCATTGAT; qRP1, TCCCCATACTTTCCCATCA-GTG; qFP2, GTGCTCAAAACCCCCAAGTAGAG; qRP2, C-ACAGTGGCTCACGCCTGT; qFP3, ACCCCCAAGTAG-AGACGAG; qRP3, TCTCGCGAACTGCCATCTG; qFP MXA , ACCTGATGGCCTATCACCAG; and qRP MXA , TTCAGGA-GCCAGCTGTAGGT.…”

Section: Sample Preparation For Gene Expression Analysis-all Human Timentioning

confidence: 99%

Secreted Histidyl-tRNA Synthetase Splice Variants Elaborate Major Epitopes for Autoantibodies in Inflammatory Myositis

Zhou

Wang

et al. 2014

Journal of Biological Chemistry

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Background: Autoantibodies (anti-Jo-1) to cytoplasmic histidyl-tRNA synthetase (HisRS) are associated with inflammatory myositis. Results: HisRS and two splice variants (SVs) cross-react with anti-Jo-1 antibodies and are secreted; at least one SV transcript is up-regulated in dermatomyositis. Conclusion: Secreted HisRS SVs contain major epitopes of anti-Jo-1 autoantibodies. Significance: Secreted HisRS and its SVs share epitopes for potential extracellular anti-Jo-1 antibody binding.

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“…To explore this possibility, polysome-association of the splice variant-encoding mRNAs was examined [Materials and Methods as described in (24)]. Of the 48 CN mRNAs tested, all were associated with polysomes in naïve Jurkat cells (fig.…”

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confidence: 99%

Human tRNA synthetase catalytic nulls with diverse functions

Gardiner

et al. 2014

Science

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108

109

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Genetic efficiency in higher organisms depends on mechanisms to create multiple functions from single genes. To investigate this question for an enzyme family, we chose aminoacyl tRNA synthetases (AARSs). They are exceptional in their progressive and accretive proliferation of noncatalytic domains as the Tree of Life is ascended. Here we report discovery of a large number of natural catalytic nulls (CNs) for each human AARS. Splicing events retain noncatalytic domains while ablating the catalytic domain (CD) to create CNs with diverse functions. Each synthetase is converted into several new signaling proteins with biological activities ‘orthogonal’ to that of the catalytic parent. We suggest that splice variants with non-enzymatic functions may be more general, as evidenced by recent findings of other catalytically inactive splice-variant enzymes.

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Regulated Capture by Exosomes of mRNAs for Cytoplasmic tRNA Synthetases

Cited by 21 publications

References 31 publications

Extracellular RNA mediates and marks cancer progression

Extracellular RNA mediates and marks cancer progression

Secreted Histidyl-tRNA Synthetase Splice Variants Elaborate Major Epitopes for Autoantibodies in Inflammatory Myositis

Human tRNA synthetase catalytic nulls with diverse functions

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