Study on the role and mechanism of miR-2944a-5p targeting the TSL and related MAPK signaling pathways to promote the susceptibility of Anopheles dirus to Plasmodium

Malaria is one of the most serious vector-borne infectious diseases. Anopheles dirus is the important malaria vector in China. It is of great significance to unveil and clarify the interactions between the parasite and vector at the molecular level for the prevention and elimination of malaria. microRNAs have been proved to have critical physiological and pathological biology functions, serving as important regulatory factors at the post-transcription level to regulate gene expression. A genome-wide analysis of miRNA-mRNA interactions have been performed and it was discovered that the transcripts of some mosquito genes are differentially regulated by certain miRNAs in response to plasmodium berghei infection. Among them, miR-2944a-5p was the most down-regulated miRNA, and its predicted target gene TSL (Torso-like) was significantly up-regulated. Shanu Jain et al reported that miRNA2944 was expressed significantly in blood fed Anopheles stephensi (42 h), and it was also significantly down-regulated in iBF (infected blood fed) 5 d when compared with iBF 42 h. TSL is the initial member of MAPK (mitogen-activated protein kinase) signaling pathway which is critical to regulating both innate immunity and metabolism during infection. Activation of MAPK signaling pathway in the mosquito midgut could facilitate parasite infection. On the basis of comprehensive analysis of literatures and previous work results, the hypothesis was proposed that miR-2944a-5p is an important susceptibility-related miRNA, which target TSL and related MAPK signaling pathways to promote the susceptibility of Anopheles dirus to Plasmodium parasite. The function of miR-2944a-5p and its target genes TSL will be studied in Anopheles dirus physiology and immunity. The tissue specific expression and temporal expression pattern of them will also be analyzed. It is expected to clarify the relevant molecular mechanisms of Anopheles dirus miR-2944a-5p target TSL involved in the MAPK signaling pathway to regulate the susceptibility to parasite from the post-transcription level through the RNA interference, Luciferase reporter assay, western, and other experimental technologies in vivo and in vitro. This study will not only help interpreter pathogen-vector interactions, but also can provide new sight for the development of novel vector control strategies.

Project details

Basic Science

Jan 2019 — Dec 2021

$31,116

China