scholarly journals Mitochondrial tRNA-Derived Fragments and Their Contribution to Gene Expression Regulation

2021 ◽  
Vol 12 ◽  
Author(s):  
Athanasios-Nasir Shaukat ◽  
Eleni G. Kaliatsi ◽  
Vassiliki Stamatopoulou ◽  
Constantinos Stathopoulos

Mutations in human mitochondrial tRNAs (mt-tRNAs) are responsible for several and sometimes severe clinical phenotypes, classified among mitochondrial diseases. In addition, post-transcriptional modifications of mt-tRNAs in correlation with several stress signals can affect their stability similarly to what has been described for their nuclear-encoded counterparts. Many of the perturbations related to either point mutations or aberrant modifications of mt-tRNAs can lead to specific cleavage and the production of mitochondrial tRNA-derived fragments (mt-tRFs). Although mt-tRFs have been detected in several studies, the exact biogenesis steps and biological role remain, to a great extent, unexplored. Several mt-tRFs are produced because of the excessive oxidative stress which predominantly affects mitochondrial DNA integrity. In addition, mt-tRFs have been detected in various diseases with possible detrimental consequences, but also their production may represent a response mechanism to external stimuli, including infections from pathogens. Finally, specific point mutations on mt-tRNAs have been reported to impact the pool of the produced mt-tRFs and there is growing evidence suggesting that mt-tRFs can be exported and act in the cytoplasm. In this review, we summarize current knowledge on mitochondrial tRNA-deriving fragments and their possible contribution to gene expression regulation.

2021 ◽  
Vol 16 ◽  
Author(s):  
Min Yao ◽  
Caiyun Jiang ◽  
Chenglong Li ◽  
Yongxia Li ◽  
Shan Jiang ◽  
...  

Background: Mammalian genes are regulated at the transcriptional and post-transcriptional levels. These mechanisms may involve the direct promotion or inhibition of transcription via a regulator or post-transcriptional regulation through factors such as micro (mi)RNAs. Objective: This study aimed to construct gene regulation relationships modulated by causality inference-based miRNA-(transition factor)-(target gene) networks and analyze gene expression data to identify gene expression regulators. Methods: Mouse gene expression regulation relationships were manually curated from literature using a text mining method which was then employed to generate miRNA-(transition factor)-(target gene) networks. An algorithm was then introduced to identify gene expression regulators from transcriptome profiling data by applying enrichment analysis to these networks. Results: A total of 22,271 mouse gene expression regulation relationships were curated for 4,018 genes and 242 miRNAs. GEREA software was developed to perform the integrated analyses. We applied the algorithm to transcriptome data for synthetic miR-155 oligo-treated mouse CD4+ T-cells and confirmed that miR-155 is an important network regulator. The software was also tested on publicly available transcriptional profiling data for Salmonella infection, resulting in the identification of miR-125b as an important regulator. Conclusion: The causality inference-based miRNA-(transition factor)-(target gene) networks serve as a novel resource for gene expression regulation research, and GEREA is an effective and useful adjunct to the currently available methods. The regulatory networks and the algorithm implemented in the GEREA software package are available under a free academic license at website : http://www.thua45.cn/gerea.


2021 ◽  
Author(s):  
Jing Du ◽  
Shu-Kai Li ◽  
Liu-Yuan Guan ◽  
Zheng Guo ◽  
Jiang-Fan Yin ◽  
...  

AbstractThe left-right symmetry breaking of vertebrate embryos requires fluid flow (called nodal flow in zebrafish). However, the molecular mechanisms that mediate the asymmetric gene expression regulation under nodal flow remain elusive. In this paper, we report that heat shock factor 1 (HSF1) is asymmetrically activated in the Kuppfer’s vesicle at the early stage of zebrafish embryos in the presence of nodal flow. Deficiency in HSF1 expression caused a significant situs inversus and disrupted gene expression asymmetry of nodal signaling proteins in zebrafish embryos. Further studies demonstrated that HSF1 could be immediately activated by fluid shear stress. The mechanical sensation ability of HSF1 is conserved in a variety of mechanical stimuli in different cell types. Moreover, cilia and the Ca2+-Akt signaling axis are essential for the activation of HSF1 under mechanical stress in vitro and in vivo. Considering the conserved expression of HSF1 in organisms, these findings unveil a fundamental mechanism of gene expression regulation triggered by mechanical clues during embryonic development and other physiological and pathological transformations.


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