基因Spring1,也称为C12orf49,是一种重要的基因,它在植物和哺乳动物中发挥重要作用。在植物中,Spring1与开花时间调控有关。例如,在模式植物蒺藜苜蓿(Medicago truncatula)中,Spring1突变体表现出单基因、显性早花表型。通过连锁分析,Spring1被定位到染色体7上,该区域包含三个FLOWERING LOCUS T (FT)基因。进一步的研究表明,Spring1突变体中FTa1基因的表达上调,而FTa1是开花时间调控的关键基因。此外,Spring1突变体中FRUITFULLb (FULb)和SUPPRESSOR OF OVER EXPRESSION OF CONSTANS1a (SOC1a)基因的表达也上调,这表明这些基因的差异表达可能是由FTa1表达增加引起的[2]。
在哺乳动物中,C12orf49,也称为SPRING,是SREBP(sterol-regulatory element binding proteins)信号通路的关键调节因子。SREBP是脂质代谢的关键转录调节因子。SPRING通过与膜结合转录因子肽酶1(MBTPS1,也称为site 1 protease)结合,促进MBTPS1的成熟,进而激活SREBP信号通路。SPRING的缺失会导致SREBP信号通路的减弱,表现为SREBP前体蛋白不能被有效切割并转运到细胞核中,从而降低SREBP靶基因的表达。此外,SPRING还参与调控胆固醇代谢,其缺失会导致胆固醇代谢紊乱。在人类癌症细胞系中,SPRING的缺失会导致细胞对脂质摄取的依赖性增加,这表明SPRING可能在肿瘤细胞代谢适应中发挥重要作用[1][3][4][5][6]。
综上所述,基因Spring1在植物和哺乳动物中发挥重要作用。在植物中,Spring1参与开花时间的调控;在哺乳动物中,C12orf49/SPRING是SREBP信号通路的关键调节因子,参与调控脂质代谢和胆固醇代谢。SPRING的研究有助于深入理解开花时间调控和脂质代谢的分子机制,为植物育种和人类疾病的治疗提供新的思路和策略。
参考文献:
1. Aregger, Michael, Lawson, Keith A, Billmann, Maximillian, Boone, Charles, Moffat, Jason. 2020. Systematic mapping of genetic interactions for de novo fatty acid synthesis identifies C12orf49 as a regulator of lipid metabolism. In Nature metabolism, 2, 499-513. doi:10.1038/s42255-020-0211-z. https://pubmed.ncbi.nlm.nih.gov/32694731/
2. Yeoh, Chin Chin, Balcerowicz, Martin, Zhang, Lulu, Ratet, Pascal, Putterill, Joanna. 2013. Fine mapping links the FTa1 flowering time regulator to the dominant spring1 locus in Medicago. In PloS one, 8, e53467. doi:10.1371/journal.pone.0053467. https://pubmed.ncbi.nlm.nih.gov/23308229/
3. Xiao, Jian, Xiong, Yanni, Yang, Liu-Ting, Luo, Jie, Song, Bao-Liang. 2020. POST1/C12ORF49 regulates the SREBP pathway by promoting site-1 protease maturation. In Protein & cell, 12, 279-296. doi:10.1007/s13238-020-00753-3. https://pubmed.ncbi.nlm.nih.gov/32666500/
4. Jaudal, Mauren, Yeoh, Chin C, Zhang, Lulu, Ratet, Pascal, Putterill, Joanna. 2013. Retroelement insertions at the Medicago FTa1 locus in spring mutants eliminate vernalisation but not long-day requirements for early flowering. In The Plant journal : for cell and molecular biology, 76, 580-91. doi:10.1111/tpj.12315. https://pubmed.ncbi.nlm.nih.gov/23964816/
5. Bayraktar, Erol C, La, Konnor, Karpman, Kara, Basu, Sumanta, Birsoy, Kıvanç. 2020. Metabolic coessentiality mapping identifies C12orf49 as a regulator of SREBP processing and cholesterol metabolism. In Nature metabolism, 2, 487-498. doi:10.1038/s42255-020-0206-9. https://pubmed.ncbi.nlm.nih.gov/32694732/
6. Loregger, Anke, Raaben, Matthijs, Nieuwenhuis, Joppe, Brummelkamp, Thijn, Zelcer, Noam. 2020. Haploid genetic screens identify SPRING/C12ORF49 as a determinant of SREBP signaling and cholesterol metabolism. In Nature communications, 11, 1128. doi:10.1038/s41467-020-14811-1. https://pubmed.ncbi.nlm.nih.gov/32111832/