Flies lacking the microRNA mir-137 exhibit increased body weight, enhanced levels of triglycerides, decreased activity, and prolonged survival under nutrient stress (starvation resistance); they also exhibit a dramatic reduction in levels of the phosphorylated/activated insulin receptor (InR in flies).
The orthologous gene in human is MIR137; the postulated roles of this microRNA are many. In vertebrates, MIR137/miR-137 has been associated with neuronal function and proliferation; it has been implicated in development of schizophrenia and other psychiatric disorders. There is also evidence that MIR137 acts as a tumor suppressor. This work in flies adds a role in maintenance of normal insulin signaling.
It was determined that one of the predicted targets of Dmel\mir-137 is Dmel\Ptp61F, the Drosophila homolog of mammalian PTPN1 and PTPN2. PTPN1 and PTPN2 are known to negatively regulate insulin signaling by dephosphorylating insulin receptor kinase (INSR). Human PTPN1 has been implicated in susceptibility to insulin resistance (MIM:176885). The Hsap\PTPN2 has been introduced into flies, but has not been characterized in the context of this disease model.
In flies, animals lacking mir-137 exhibit increased levels of Ptp61F. Direct overexpression of Ptp61F results in phenotypes similar to loss of mir-137 : reduction in InR-P, enhanced starvation resistance, increased body weight, and increased triglyceride levels. Neural-specific knockdown of Ptp61F, effected by RNAi, ameliorates most phenotypes of mir-137 null mutations.
[updated Mar. 2024 by FlyBase; FBrf0222196]
Flies lacking mir-137 exhibit increased body weight, enhanced levels of triglycerides, decreased activity, and starvation resistance (FBrf0258572).
In mouse, miR-137 has been shown to regulate neural stem cell proliferation and differentiation in mouse embryonic stem cells, and neuronal maturation in later stages. In human, MIR137 has been implicated to act as a tumor suppressor in several cancer types. Recent genome-wide association studies have provided evidence that single nucleotide polymorphisms in the vicinity of the MIR137 gene may be associated with schizophrenia and other psychiatric disorders. [https://rfam.org/family/RF00694 2024.03.05]
PTPN1 and PTPN2 encode non-receptor type tyrosine-specific phosphatases that dephosphorylate multiple receptor protein tyrosine kinases including INSR. [GeneCards PTPN1, PTPN2; 2024.03.05]
Many to one: 2 human genes to 1 Drosophila gene; additional less closely related genes in both species.
Many to one: 2 human genes to 1 Drosophila gene; additional less closely related genes in both species.
One to one: 1 human gene to 1 Drosophila gene.
High-scoring ortholog of human PTPN2 and PTPN1 (1 Drosophila to 2 human; additional less closely related genes in both species).
Ortholog of human microRNA MIR137; 87% identity (FBrf0215696).
