Dynamic miRNA-mRNA interactions coordinate gene expression in adult Anopheles gambiae

Autoři: Xiaonan Fu aff001;  Pengcheng Liu aff002;  George Dimopoulos aff003;  Jinsong Zhu aff002
Působiště autorů: The Interdisciplinary Ph.D. Program in Genetics, Bioinformatics, and Computational Biology, Virginia Tech, Blacksburg, Virginia, United States of America aff001;  Department of Biochemistry, Virginia Tech, Blacksburg, Virginia, United States of America aff002;  W. Harry Feinstone Department of Molecular Microbiology and Immunology, Bloomberg School of Public Health, Johns Hopkins University, Baltimore, Maryland, United States of America aff003
Vyšlo v časopise: Dynamic miRNA-mRNA interactions coordinate gene expression in adult Anopheles gambiae. PLoS Genet 16(4): e32767. doi:10.1371/journal.pgen.1008765
Kategorie: Research Article
doi: https://doi.org/10.1371/journal.pgen.1008765


microRNAs (miRNAs) are increasingly recognized as important regulators of many biological processes in mosquitoes, vectors of numerous devastating infectious diseases. Identification of bona fide targets remains the bottleneck for functional studies of miRNAs. In this study, we used CLEAR-CLIP assays to systematically analyze miRNA-mRNA interactions in adult female Anopheles gambiae mosquitoes. Thousands of miRNA-target pairs were captured after direct ligation of the miRNA and its cognate target transcript in endogenous Argonaute–miRNA–mRNA complexes. Using two interactions detected in this manner, miR-309-SIX4 and let-7-kr-h1, we demonstrated the reliability of this experimental approach in identifying in vivo gene regulation by miRNAs. The miRNA-mRNA interaction dataset provided an invaluable opportunity to decipher targeting rules of mosquito miRNAs. Enriched motifs in the diverse targets of each miRNA indicated that the majority of mosquito miRNAs rely on seed-based canonical target recognition, while noncanonical miRNA binding sites are widespread and often contain motifs complementary to the central or 3’ ends of miRNAs. The time-lapse study of miRNA-target interactomes in adult female mosquitoes revealed dynamic miRNA regulation of gene expression in response to varying nutritional sources and physiological demands. Interestingly, some miRNAs exhibited flexibility to use distinct sequences at different stages for target recognition. Furthermore, many miRNA-mRNA interactions displayed stage-specific patterns, especially for those genes involved in metabolism, suggesting that miRNAs play critical roles in precise control of gene expression to cope with enormous physiological demands associated with egg production. The global mapping of miRNA-target interactions contributes to our understanding of miRNA targeting specificity in non-model organisms. It also provides a roadmap for additional studies focused on regulatory functions of miRNAs in Anopheles gambiae.

Klíčová slova:

Blood – Gene expression – Luciferase – Messenger RNA – MicroRNAs – Mosquitoes – RNA sequencing – Sequence motif analysis


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