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SR 蛋白 RSP-2 影响截短胰岛素受体 DAF-2B 在秀丽隐杆线虫中的表达。

The SR protein RSP-2 influences expression of the truncated insulin receptor DAF-2B in Caenorhabditis elegans.

机构信息

Institute on the Biology of Aging and Metabolism and the Department of Genetics, Cell Biology and Development, University of Minnesota, 4-114 Nils Hasselmo Hall, 312 Church Street SE, Minneapolis, MN 55455, USA.

出版信息

G3 (Bethesda). 2023 Jun 1;13(6). doi: 10.1093/g3journal/jkad064.

DOI:10.1093/g3journal/jkad064
PMID:36966398
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC10234397/
Abstract

The alternatively spliced daf-2b transcript in Caenorhabditis elegans encodes a truncated isoform of the nematode insulin receptor that retains the extracellular ligand binding domain but lacks the intracellular signaling domain and is therefore unable to transduce a signal. To identify factors that influence expression of daf-2b, we performed a targeted RNA interference screen of rsp genes, which encode splicing factors from the serine/arginine protein family. Loss of rsp-2 significantly increased the expression of a fluorescent daf-2b splicing reporter, as well as increasing expression of endogenous daf-2b transcripts. Correspondingly, rsp-2 mutants exhibited similar phenotypes to those previously observed with DAF-2B overexpression, namely suppression of pheromone-induced dauer formation, enhancement of dauer entry in insulin signaling mutants, inhibition of dauer recovery, and increased lifespan. However, the epistatic relationship between rsp-2 and daf-2b varied according to the experimental context. Increased dauer entry and delayed dauer exit of rsp-2 mutants in an insulin signaling mutant background were partially dependent on daf-2b. Conversely, suppression of pheromone-induced dauer formation and increased lifespan in rsp-2 mutants were independent of daf-2b. These data demonstrate that C. elegans RSP-2, an ortholog of human splicing factor protein SRSF5/SRp40, is involved in regulating the expression of the truncated DAF-2B isoform. However, we also find that RSP-2 can influence dauer formation and lifespan independently of DAF-2B.

摘要

在秀丽隐杆线虫中，选择性剪接的 daf-2b 转录本编码了一种截短的线虫胰岛素受体同工型，该同工型保留了细胞外配体结合域，但缺乏细胞内信号转导域，因此无法传递信号。为了鉴定影响 daf-2b 表达的因素，我们对 rsp 基因进行了靶向 RNA 干扰筛选，rsp 基因编码丝氨酸/精氨酸蛋白家族的剪接因子。rsp-2 的缺失显著增加了荧光 daf-2b 剪接报告的表达，同时也增加了内源性 daf-2b 转录本的表达。相应地，rsp-2 突变体表现出与 DAF-2B 过表达之前观察到的相似表型，即抑制信息素诱导的 dauer 形成，增强胰岛素信号突变体中的 dauer 进入，抑制 dauer 恢复，并延长寿命。然而，rsp-2 和 daf-2b 之间的上位性关系因实验背景而异。在胰岛素信号突变体背景下，rsp-2 突变体 dauer 进入增加和 dauer 退出延迟部分依赖于 daf-2b。相反，rsp-2 突变体中信息素诱导 dauer 形成的抑制和寿命的延长独立于 daf-2b。这些数据表明，秀丽隐杆线虫 RSP-2 是人类剪接因子蛋白 SRSF5/SRp40 的同源物，参与调节截短的 DAF-2B 同工型的表达。然而，我们还发现 RSP-2 可以独立于 DAF-2B 影响 dauer 形成和寿命。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4912/10234397/68a43833f172/jkad064f8.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4912/10234397/650adc9fb4d7/jkad064f1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4912/10234397/fb434a12014e/jkad064f2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4912/10234397/10e4b14e6ae6/jkad064f3.jpg
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https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4912/10234397/6d6b108d700e/jkad064f5.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4912/10234397/57bd155728eb/jkad064f6.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4912/10234397/c0f9b531882e/jkad064f7.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4912/10234397/68a43833f172/jkad064f8.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4912/10234397/650adc9fb4d7/jkad064f1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4912/10234397/fb434a12014e/jkad064f2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4912/10234397/10e4b14e6ae6/jkad064f3.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4912/10234397/4088c6b799b7/jkad064f4.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4912/10234397/6d6b108d700e/jkad064f5.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4912/10234397/57bd155728eb/jkad064f6.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4912/10234397/c0f9b531882e/jkad064f7.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4912/10234397/68a43833f172/jkad064f8.jpg

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