干燥综合征抗原 B 在秀丽隐杆线虫和人类中调节 LIN28-let-7 轴。

Sjögren Syndrome antigen B regulates LIN28-let-7 axis in Caenorhabditis elegans and human.

机构信息

Disease Target Structure Research Center, Korea Research Institute of Bioscience and Biotechnology, Daejeon 34141, Republic of Korea; Department of Biomolecular Science, KRIBB School of Biological Science, Korea University of Science and Technology, Daejeon 34113, Republic of Korea.

Disease Target Structure Research Center, Korea Research Institute of Bioscience and Biotechnology, Daejeon 34141, Republic of Korea; College of Pharmacy, Chungbuk National University, Cheongju 34113, Republic of Korea.

出版信息

Biochim Biophys Acta Gene Regul Mech. 2021 Mar;1864(3):194684. doi: 10.1016/j.bbagrm.2021.194684. Epub 2021 Jan 21.

DOI:10.1016/j.bbagrm.2021.194684

PMID:33484878

Abstract

LIN28 protein and let-7 family micro RNAs (miRNAs) that are an evolutionarily conserved from nematodes to humans are the important regulators of developmental timing by dynamically interacting with each other. However, regulators of LIN28 remain largely elusive. Here, we show the evidences that Sjögren Syndrome antigen B (SSB) protein associates and cooperates with LIN28A and LIN28B, mammalian orthologues of Caenorhabditis elegans lin-28, proteins in the nucleus. Knockdown of SSB in HEK293 cell line resulted in the decrease of the amount of LIN28B mRNAs and proteins, and the increase of the level of mature let-7 miRNAs. Furthermore, RNA interference of ssb-1 gene, a worm SSB orthologue, was sufficient to cause a heterochronic defect in seam cells of C. elegans, recapitulating the phenotype of lin-28 downregulation. Collectively, we suggest that SSB is an important regulator for the LIN28-let-7 axis.

摘要

LIN28 蛋白和 let-7 家族 microRNAs（miRNAs）是从线虫到人高度保守的重要发育时序调控因子，它们通过相互动态作用。然而，LIN28 的调控因子在很大程度上仍未被发现。在这里，我们展示了证据表明干燥综合征抗原 B（SSB）蛋白与 LIN28A 和 LIN28B 相关，并与它们相互作用，LIN28A 和 LIN28B 是线虫 lin-28 的哺乳动物同源物，是细胞核内的蛋白质。在 HEK293 细胞系中敲低 SSB 会导致 LIN28B mRNAs 和蛋白质的数量减少，以及成熟 let-7 miRNAs 的水平增加。此外，线虫 SSB 同源物 ssb-1 基因的 RNA 干扰足以导致线虫 seam 细胞的异时性缺陷，再现了 lin-28 下调的表型。总之，我们认为 SSB 是 LIN28-let-7 轴的重要调节因子。