Dataset Information

Mosquito-specific microRNA-1174 targets serine hydroxymethyltransferase to control key functions in the gut.

ABSTRACT: Lineage-specific microRNAs (miRNAs) may contribute to functions specific to hematophagous mosquitoes and, as such, have potential for contributing to the development of future mosquito control approaches. Here we report that the mosquito- and gut-specific miRNA, miR-1174, is required for proper sugar absorption, fluid excretion, blood intake, and, consequently, egg maturation and survival in female mosquitoes. miR-1174 is highly expressed and localized in the posterior midgut, the blood-digesting portion of the mosquito alimentary canal. Depletion of miR-1174 results in severe defects in sugar absorption and blood intake. We identified serine hydroxymethyltransferase (SHMT) is a direct miR-1174 target. The adverse phenotypes caused by miR-1174 silencing were rescued by SHMT RNA interference. Our results suggest that miR-1174 is essential for fine-tuning the SHMT transcript to levels necessary for normal mosquito gut functions.

SUBMITTER: Liu S

PROVIDER: S-EPMC4209991 | biostudies-literature | 2014 Oct

REPOSITORIES: biostudies-literature

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Mosquito-specific microRNA-1174 targets serine hydroxymethyltransferase to control key functions in the gut.

Liu Shiping S Lucas Keira J KJ Roy Sourav S Ha Jisu J Raikhel Alexander S AS

Proceedings of the National Academy of Sciences of the United States of America 20140922 40

Lineage-specific microRNAs (miRNAs) may contribute to functions specific to hematophagous mosquitoes and, as such, have potential for contributing to the development of future mosquito control approaches. Here we report that the mosquito- and gut-specific miRNA, miR-1174, is required for proper sugar absorption, fluid excretion, blood intake, and, consequently, egg maturation and survival in female mosquitoes. miR-1174 is highly expressed and localized in the posterior midgut, the blood-digestin ...[more]

PMID: 25246546

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Project description:Serine hydroxymethyltransferase (SHMT), encoded by the glyA gene, is a ubiquitous pyridoxal 5'-phosphate (PLP)-dependent enzyme that catalyzes the formation of glycine from serine. The thereby generated 5,10-methylene tetrahydrofolate (MTHF) is a major source of cellular one-carbon units and a key intermediate in thymidylate biosynthesis. While in virtually all eukaryotic and many bacterial systems thymidylate synthase ThyA, SHMT and dihydrofolate reductase (DHFR) are part of the thymidylate/folate cycle, the situation is different in organisms using flavin-dependent thymidylate synthase ThyX. Here the distinct catalytic reaction directly produces tetrahydrofolate (THF) and consequently in most ThyX-containing organisms, DHFR is absent. While the resulting influence on the folate metabolism of ThyX-containing bacteria is not fully understood, the presence of ThyX may provide growth benefits under conditions where the level of reduced folate derivatives is compromised. Interestingly, the third key enzyme implicated in generation of MTHF, serine hydroxymethyltransferase (SHMT), has a universal phylogenetic distribution, but remains understudied in ThyX-containg bacteria. To obtain functional insight into these ThyX-dependent thymidylate/folate cycles, we characterized the predicted SHMT from the ThyX-containing bacterium Helicobacter pylori. Serine hydroxymethyltransferase activity was confirmed by functional genetic complementation of a glyA-inactivated E. coli strain. A H. pylori ΔglyA strain was obtained, but exhibited markedly slowed growth and had lost the virulence factor CagA. Biochemical and spectroscopic evidence indicated formation of a characteristic enzyme-PLP-glycine-folate complex and revealed unexpectedly weak binding affinity of PLP. The three-dimensional structure of the H. pylori SHMT apoprotein was determined at 2.8Ǻ resolution, suggesting a structural basis for the low affinity of the enzyme for its cofactor. Stabilization of the proposed inactive configuration using small molecules has potential to provide a specific way for inhibiting HpSHMT.

Dataset Information

Mosquito-specific microRNA-1174 targets serine hydroxymethyltransferase to control key functions in the gut.

Publications

Mosquito-specific microRNA-1174 targets serine hydroxymethyltransferase to control key functions in the gut.

Similar Datasets

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