Emerson James I, Shi Wei, Paredes-Larios Jose, Walker William G, Hutton Josiah E, Cristea Ileana M, Marzluff William F, Conlon Frank L
Department of Biochemistry & Biophysics (J.I.E., W.F.M.), University of North Carolina, Chapel Hill.
Department of Biology and Genetics, McAllister Heart Institute (W.S., J.P.-L., W.G.W., W.F.M., F.L.C.), University of North Carolina, Chapel Hill.
Circ Res. 2025 Jan 31;136(3):258-275. doi: 10.1161/CIRCRESAHA.124.325447. Epub 2024 Dec 30.
Males and females exhibit distinct anatomic and functional characteristics of the heart, predisposing them to specific disease states.
We identified microRNAs (miRNAs/miR) with sex-differential expression in mouse hearts.
Four conserved miRNAs are present in a single locus on the X-chromosome and are expressed at higher levels in females than males. We show miRNA, miR-871, is responsible for decreased expression of the protein SRL (sarcalumenin) in females. SRL is involved in calcium signaling, and we show it contributes to differences in electrophysiology between males and females. miR-871 overexpression mimics the effects of the cardiac physiology of conditional cardiomyocyte-specific Srl-null mice. Inhibiting miR-871 with an antagomir in females shortened ventricular repolarization. The human orthologue of miR-871, miR-888, coevolved with the SRL 3' untranslated region and regulates human SRL.
These data highlight the importance of sex-differential miRNA mechanisms in mediating sex-specific functions and their potential relevance to human cardiac diseases.
男性和女性的心脏表现出不同的解剖和功能特征，使他们易患特定的疾病状态。
我们在小鼠心脏中鉴定出具有性别差异表达的微小RNA（miRNA/miR）。
四个保守的miRNA位于X染色体上的一个单一基因座中，在雌性中的表达水平高于雄性。我们发现miRNA，即miR-871，是导致雌性中蛋白质SRL（肌浆网素）表达降低的原因。SRL参与钙信号传导，并且我们表明它导致了雄性和雌性之间电生理的差异。miR-871的过表达模拟了条件性心肌细胞特异性Srl基因敲除小鼠的心脏生理学效应。在雌性中用抗miR抑制miR-871缩短了心室复极化。miR-871的人类同源物miR-888与SRL 3'非翻译区共同进化并调节人类SRL。
这些数据突出了性别差异miRNA机制在介导性别特异性功能中的重要性及其与人类心脏疾病的潜在相关性。
