# Serine Hydroxymethyltransferase Modulates Midgut Physiology in Aedes aegypti Through miRNA Regulation: Insights from Small RNA Sequencing and Gene Expression Analysis

## TL;DR

This study shows how SHMT, an enzyme in mosquitoes, affects midgut function by regulating specific miRNAs, offering new insights into mosquito biology and control.

## Contribution

The study reveals a novel link between SHMT and miRNA regulation in the mosquito midgut, influencing digestion and metabolism.

## Key findings

- SHMT silencing alters the expression of specific miRNAs like miR-2940-5p and miR-306-5p in Aedes aegypti midguts.
- Key miRNA biogenesis enzymes such as Drosha, Dicer1, and AGO1 show significant expression changes after SHMT downregulation.
- SHMT appears to modulate midgut physiology through miRNA regulation, impacting digestion and nutritional metabolism.

## Abstract

Aedes aegypti mosquitoes are critical vectors of arboviruses, responsible for transmitting pathogens that pose significant public health challenges. Serine hydroxymethyltransferase (SHMT), a key enzyme in one-carbon metabolism, plays a vital role in various biological processes, including DNA synthesis, energy metabolism, and cell proliferation. Although SHMT is expressed at low levels in the midgut of Aedes aegypti, its silencing has been shown to inhibit blood meal digestion. The precise mechanisms by which SHMT regulates midgut physiology in mosquitoes remain poorly understood. In this study, we employed small RNA sequencing and quantitative PCR to identify differentially expressed miRNAs (DEMs) following SHMT downregulation. We focused on a subset of DEMs—miR-2940-5p, miR-2940-3p, miR-2941, and miR-306-5p—to explore their potential biological functions. To further elucidate the molecular mechanisms underlying the miRNA response to SHMT downregulation, we analyzed the expression levels of key genes involved in the miRNA biogenesis pathway. Our results demonstrated that several critical enzymes, including Drosha, Dicer1, and AGO1, exhibited significant changes in expression upon SHMT silencing. This study provides new insights into the molecular mechanisms through which SHMT influences the biological functions and nutritional metabolism of the mosquito midgut. By linking SHMT activity to miRNA regulation, our findings highlight a potential pathway by which SHMT modulates midgut physiology, offering a foundation for future research into mosquito biology and vector control strategies.