Mosquito-specific microRNA-1174 targets serine hydroxymethyltransferase to control key functions in the gut
Mosquito-specific microRNA-1174 targets serine hydroxymethyltransferase to control key functions in the gut
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蚊子特异性 microRNA-1174 靶向丝氨酸羟甲基转移酶以控制肠道关键功能
DOI：
10.1073/pnas.1416278111
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发表时间：
2014-10-07
影响因子：
11.1
通讯作者：
Raikhel, Alexander S.
中科院分区：
文献类型：
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作者：
Liu, Shiping;Lucas, Keira J.;Raikhel, Alexander S.
重要意义几种蚊子的雌性蚊子进化出了必须的吸血方式，以提供卵子发育所需的氨基酸和其他营养物质，这为许多毁灭性疾病在人类中的传播提供了机制。蚊子特异的microRNA(MiRNA)miR-1174在血餐后显著上调，并特异于雌性蚊子中肠，表明在血餐相关事件中发挥了作用。我们已经发现miR-1174以丝氨酸羟甲基转移酶为靶标，是埃及伊蚊和冈比亚按蚊关键功能所必需的。它的抑制作用扰乱了糖的吸收、液体的排泄、肠道中的血液吸收，从而破坏了卵子的成熟和存活。蚊子特有的miRNAs，如miR-1174，有可能影响下一代蚊子控制的发展。谱系特异的microRNAs(MiRNAs)可能有助于食血蚊子特有的功能，因此有可能有助于未来蚊子控制方法的发展。在这里，我们报告了蚊子和肠道特异的miRNA，miR-1174，是适当的糖吸收、液体排泄、血液吸收所必需的，因此，雌性蚊子的卵成熟和存活是必需的。MIR-1174高表达并定位于蚊子消化道的后中肠，即蚊子消化血液的部分。MiR-1174的耗尽会导致糖吸收和血液摄入的严重缺陷。我们发现丝氨酸羟甲基转移酶(SHMT)是miR-1174的直接靶点。通过SHMT RNA干扰挽救miR-1174沉默引起的不良表型。我们的结果表明miR-1174对于将SHMT转录本微调到正常蚊子肠道功能所需的水平是必不可少的。
Significance Females of several mosquito species have evolved obligatory blood-feeding to supply amino acids and other nutrients necessary for egg development, providing a mechanism for the spread of many devastating diseases in humans. The mosquito-specific microRNA (miRNA), miR-1174, is significantly upregulated post blood meal and specific to the female mosquito midgut, suggesting a role in blood meal-associated events. We have found that miR-1174 targets serine hydroxymethyltransferase and is required for key functions in Aedes aegypti and Anopheles gambiae. Its inhibition disrupts sugar absorption, fluid excretion, blood intake in the gut, and, consequently, egg maturation and survival. Mosquito-specific miRNAs, such as miR-1174, have the potential for influencing the development of a future generation of mosquito control. 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.