Modulation of insulin secretion by RBFOX2-mediated alternative splicing.
Modulation of insulin secretion by RBFOX2-mediated alternative splicing.
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DOI：
10.1038/s41467-023-43605-4
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发表时间：
2023-11-25
影响因子：
16.6
通讯作者：
Sussel, Lori
中科院分区：
文献类型：
--
作者：
Moss, Nicole D.;Wells, Kristen L.;Theis, Alexandra;Kim, Yong-Kyung;Spigelman, Aliya F.;Liu, Xiong;Macdonald, Patrick E.;Sussel, Lori
胰岛素分泌是一个严格调节的过程，对于维持血糖稳态至关重要。尽管胰岛素颗粒运输和分泌的分子成分已被充分确定，但如何调节它们以快速微调分泌以响应不断变化的环境条件尚不清楚。最近的研究已经确定，RNA 结合蛋白 (RBP) 失调和异常 mRNA 剪接发生在糖尿病发病时。我们通过胰岛素颗粒对接和胞吐作用所需基因的选择性剪接证明，RBP（RBFOX2）是胰岛素分泌的关键调节因子。小鼠胰腺中 Rbfox2 的条件性突变会导致胰岛素分泌减少和血糖稳态受损。与分泌缺陷一致，我们观察到 SNARE 复合体组件中胰岛素颗粒对接减少和相应的剪接缺陷。这些发现确定了调节健康和功能失调的胰腺 β 细胞中胰岛素分泌的额外机制。胰腺β细胞分泌胰岛素是一个受到严格调控的过程，对于维持血糖稳态至关重要。在这里，作者表明，RNA 结合蛋白 RBFOX2 通过胰岛素颗粒对接和胞吐作用所需基因的选择性剪接来调节胰岛素分泌。
Insulin secretion is a tightly regulated process that is vital for maintaining blood glucose homeostasis. Although the molecular components of insulin granule trafficking and secretion are well established, how they are regulated to rapidly fine-tune secretion in response to changing environmental conditions is not well characterized. Recent studies have determined that dysregulation of RNA-binding proteins (RBPs) and aberrant mRNA splicing occurs at the onset of diabetes. We demonstrate that the RBP, RBFOX2, is a critical regulator of insulin secretion through the alternative splicing of genes required for insulin granule docking and exocytosis. Conditional mutation of Rbfox2 in the mouse pancreas results in decreased insulin secretion and impaired blood glucose homeostasis. Consistent with defects in secretion, we observe reduced insulin granule docking and corresponding splicing defects in the SNARE complex components. These findings identify an additional mechanism for modulating insulin secretion in both healthy and dysfunctional pancreatic β cells. Insulin secretion from the pancreatic beta cell is a tightly regulated process that is vital for maintaining blood glucose homeostasis. Here, the authors show that the RNA binding protein RBFOX2 is a regulator of insulin secretion through the alternative splicing of genes required for insulin granule docking and exocytosis.
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影响因子：
9.3
作者：
Baron M;Veres A;Wolock SL;Faust AL;Gaujoux R;Vetere A;Ryu JH;Wagner BK;Shen-Orr SS;Klein AM;Melton DA;Yanai I
通讯作者：
Yanai I
影响因子：
16.2
作者：
Jacko M;Weyn-Vanhentenryck SM;Smerdon JW;Yan R;Feng H;Williams DJ;Pai J;Xu K;Wichterle H;Zhang C
通讯作者：
Zhang C
影响因子：
4.5
作者：
Johansson JU;Ericsson J;Janson J;Beraki S;Stanić D;Mandic SA;Wikström MA;Hökfelt T;Ogren SO;Rozell B;Berggren PO;Bark C
通讯作者：
Bark C
影响因子：
2.5
作者：
Daraio, Teresa;Valladolid-Acebes, Ismael;Bark, Christina
通讯作者：
Bark, Christina
影响因子：
50.3
作者：
Hingorani, SR;Petricoin, EF;Tuveson, DA
通讯作者：
Tuveson, DA