miR-34c-3p Regulates Protein Kinase A Activity Independent of cAMP by Dicing
            <i>prkar2b</i>
            Transcripts in Theileria annulata-Infected Leukocytes

Haidar, Malak; Tajeri, Shahin; Momeux, Laurence; Mourier, Tobias; Rached, Fathia Ben; Mfarrej, Sara; Rchiad, Zineb; Pain, Arnab; Langsley, Gordon

doi:10.1128/msphere.00526-22

Cited by 2 publications

(2 citation statements)

References 27 publications

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“…Research has shown that miR-34c-3p plays a regulatory role in cAMP-independent regulation of host cell protein kinase A (PKA) activity in Theileria annulata -infected bovine red blood cells. The discovery of this mechanism has important reference value for the prevention and control of diseases caused by Theileria annulata [ 27 ]. Although research on miRNA regulation of target gene function is still very limited, existing studies have confirmed that miRNA molecules can play an important regulatory role in pathogenic infections of the host [ 28 ].…”

Section: Introductionmentioning

confidence: 99%

Role of Recognition MicroRNAs in Hemaphysalis longicornis and Theileria orientalis Interactions

Luo,

Tan,

Zhao

et al. 2024

Pathogens

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Ticks are an important type of pathogen transmission vector, and pathogens not only cause serious harm to livestock but can also infect humans. Because of the roles that ticks play in disease transmission, reducing tick pathogen infectivity has become increasingly important and requires the identification and characterization of these pathogens and their interaction mechanisms. In this study, we determined the miRNA expression profile of Hemaphysalis longicornis infected with Theileria orientalis, predicted the target genes of miRNAs involved in this infection process, and investigated the role of miRNA target recognition during host–pathogen interactions. The results showed that longipain is a target gene of miR-5309, which was differentially expressed at different developmental stages and in various tissues in the control group. However, the miR-5309 level was reduced in the infection group. Analysis of the interaction between miRNA and the target gene showed that miR-5309 negatively regulated the expression of the longipain protein during the infection of H. longicornis with T. orientalis. To verify this inference, we compared longipain with the blocking agent orientalis. In this study, the expression of longipain was upregulated by the inhibition of miR-5309 in ticks, and the ability of the antibody produced by the tick-derived protein to attenuate T. orientalis infection was verified through animal immunity and antigen–antibody binding tests. The results showed that expression of the longipain + GST fusion protein caused the cattle to produce antibodies that could be successfully captured by ticks, and cellular immunity was subsequently activated in the ticks, resulting in a subtractive effect on T. orientalis infection. This research provides ideas for the control of ticks and tickborne diseases and a research basis for studying the mechanism underlying the interaction between ticks and pathogens.

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Section: Introductionmentioning

confidence: 99%

Role of Recognition MicroRNAs in Hemaphysalis longicornis and Theileria orientalis Interactions

Luo,

Tan,

Zhao

et al. 2024

Pathogens

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“…Downregulated expression of another host factor, Transforming growth factor-beta 2 (TGF-ß2), has also been linked to reduced dissemination potential of attenuated cells 30 . Recently, downregulated expression of infection-induced microRNAs mir-126-5p and mir34c-3p was shown to contribute to reduced Matrigel traversal of attenuated macrophages 31 , 32 .…”

Section: Introductionmentioning

confidence: 99%

Dual RNA-seq to catalogue host and parasite gene expression changes associated with virulence of T. annulata-transformed bovine leukocytes: towards identification of attenuation biomarkers

Elati,

Tajeri,

Obara

et al. 2023

Sci Rep

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The apicomplexan parasite Theileria annulata is transmitted by Hyalomma ticks and causes an acute lymphoproliferative disease that is invariably lethal in exotic cattle breeds. The unique ability of the schizont stage of T. annulata to transform infected leukocytes to a cancer-like phenotype and the simplicity of culturing and passaging T. annulata-transformed cells in vitro have been explored for live vaccine development by attenuating the transformed cells using lengthy serial propagation in vitro. The empirical in vivo evaluation of attenuation required for each batch of long-term cultured cells is a major constraint since it is resource intensive and raises ethical issues regarding animal welfare. As yet, the molecular mechanisms underlying attenuation are not well understood. Characteristic changes in gene expression brought about by attenuation are likely to aid in the identification of novel biomarkers for attenuation. We set out to undertake a comparative transcriptome analysis of attenuated (passage 296) and virulent (passage 26) bovine leukocytes infected with a Tunisian strain of T. annulata termed Beja. RNA-seq was used to analyse gene expression profiles and the relative expression levels of selected genes were verified by real-time quantitative PCR (RT-qPCR) analysis. Among the 3538 T. annulata genes analysed, 214 were significantly differentially expressed, of which 149 genes were up-regulated and 65 down-regulated. Functional annotation of differentially expressed T. annulata genes revealed four broad categories of metabolic pathways: carbon metabolism, oxidative phosphorylation, protein processing in the endoplasmic reticulum and biosynthesis of secondary metabolites. It is interesting to note that of the top 40 genes that showed altered expression, 13 were predicted to contain a signal peptide and/or at least one transmembrane domain, suggesting possible involvement in host-parasite interaction. Of the 16,514 bovine transcripts, 284 and 277 showed up-regulated and down-regulated expression, respectively. These were assigned to functional categories relevant to cell surface, tissue morphogenesis and regulation of cell adhesion, regulation of leucocyte, lymphocyte and cell activation. The genetic alterations acquired during attenuation that we have catalogued herein, as well as the accompanying in silico functional characterization, do not only improve understanding of the attenuation process, but can also be exploited by studies aimed at identifying attenuation biomarkers across different cell lines focusing on some host and parasite genes that have been highlighted in this study, such as bovine genes (CD69, ZNF618, LPAR3, and APOL3) and parasite genes such as TA03875.

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miR-34c-3p Regulates Protein Kinase A Activity Independent of cAMP by Dicing prkar2b Transcripts in Theileria annulata-Infected Leukocytes

Cited by 2 publications

References 27 publications

Role of Recognition MicroRNAs in Hemaphysalis longicornis and Theileria orientalis Interactions

Role of Recognition MicroRNAs in Hemaphysalis longicornis and Theileria orientalis Interactions

Dual RNA-seq to catalogue host and parasite gene expression changes associated with virulence of T. annulata-transformed bovine leukocytes: towards identification of attenuation biomarkers

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