Defining the RNA interactome of Aedes mosquitoes

Laurent, Zaydah Rolande de (2025) Defining the RNA interactome of Aedes mosquitoes. PhD thesis, University of Glasgow.

Abstract

System-wide approaches have uncovered a vast spectrum of RNA-binding proteins (RBPs) in mammals and a few non-mammalian organisms, such as the fruit fly, zebrafish, roundworms, and plants. However, information on RBPs of arboviral vectors remains largely unknown. RNA interactome capture was used to characterise the RBPome in cells of two medically important mosquito vectors, Aedes aegypti and Aedes albopictus. 852 and 683 RBPs were identified in Aedes aegypti and Aedes albopictus, respectively. These RBPs exhibited properties similar to those of human RBPs, having low hydrophobicity that favoured solubility; basic pH to enable interactions with RNA; and contained intrinsically disordered regions, low complexity regions, such as the RGG box and poly (K) that allow for dynamically modular interactions. The use of RBDmap to map mosquito RBPs also revealed that sequence conservation was most apparent in the RNA-binding site. Underscoring the evolutionary conservation of RNA–protein interactions. Further profiling of Aedes aegypti RPBome during SINV infection using comparative (RIC) identified 219 differentially regulated proteins, seventy-two were upregulated, while 143 proteins were downregulated. Characterisation of these proteins revealed 80% lacked canonical RNA binding domains, >25% were metabolic enzymes, and GO terms identified that the proteins were involved in transport, nucleotide degradation, and energy metabolism. Lastly, knockdown of 17 differentially regulated proteins revealed that 15 of 17 candidates were proviral. Knockdown efficiency and duration of transfection influenced the phenotype of screened RBPs. XRN1 and DCP1A were found to be proviral, while AAEL010642, a PABP, was antiviral. This study provides the first comprehensive characterisation of the mosquito RBPome, revealing evolutionary conservation with other organisms, dynamic reprogramming during SINV infection, and identifying host factors that predominantly act as proviral regulators of viral replication.

• Item Type: Thesis (PhD)
• Qualification Level: Doctoral
• Subjects: Q Science > QR Microbiology > QR355 Virology
• Colleges/Schools: College of Medical Veterinary and Life Sciences > School of Infection & Immunity > Centre for Virus Research
• Supervisor's Name: Castello, Professor Alfredo, Kohl, Professor Alain and Kamel, Dr. Wael
• Date of Award: 2025
• Depositing User: Theses Team
• Unique ID: glathesis:2025-85648
• Copyright: Copyright of this thesis is held by the author.
• Date Deposited: 11 Dec 2025 11:43
• Last Modified: 11 Dec 2025 11:46
• Thesis DOI: 10.5525/gla.thesis.85648
• URI: https://theses.gla.ac.uk/id/eprint/85648