Program of Hepatology, Center for Applied Medical Research (CIMA), University of Navarra, Avda. Pio XII, n55, 31008 Pamplona, Spain.
IdiSNA, Navarra Institute for Health Research, 31008 Pamplona, Spain.
Int J Mol Sci. 2022 Nov 2;23(21):13411. doi: 10.3390/ijms232113411.
SLU7 (Splicing factor synergistic lethal with U5 snRNA 7) was first identified as a splicing factor necessary for the correct selection of 3' splice sites, strongly impacting on the diversity of gene transcripts in a cell. More recent studies have uncovered new and non-redundant roles of SLU7 as an integrative hub of different levels of gene expression regulation, including epigenetic DNA remodeling, modulation of transcription and protein stability. Here we review those findings, the multiple factors and mechanisms implicated as well as the cellular functions affected. For instance, SLU7 is essential to secure liver differentiation, genome integrity acting at different levels and a correct cell cycle progression. Accordingly, the aberrant expression of SLU7 could be associated with human diseases including cancer, although strikingly, it is an essential survival factor for cancer cells. Finally, we discuss the implications of SLU7 in pathophysiology, with particular emphasis on the progression of liver disease and its possible role as a therapeutic target in human cancer.
SLU7（与 U5 snRNA7 协同致死的剪接因子）最初被鉴定为一种剪接因子，对于正确选择 3' 剪接位点是必需的，这强烈影响了细胞中转录本的多样性。最近的研究揭示了 SLU7 的新的和非冗余作用，作为不同水平的基因表达调控的综合枢纽，包括表观遗传 DNA 重塑、转录和蛋白质稳定性的调节。在这里，我们回顾了这些发现、涉及的多种因素和机制以及受影响的细胞功能。例如，SLU7 对于确保肝脏分化、在不同水平上发挥作用的基因组完整性以及正确的细胞周期进展是必不可少的。因此，SLU7 的异常表达可能与包括癌症在内的人类疾病有关，尽管引人注目地，它是癌细胞存活的必需因子。最后，我们讨论了 SLU7 在病理生理学中的意义，特别强调了肝脏疾病的进展及其在人类癌症中作为治疗靶点的可能作用。
