The multifunctional RNA-binding protein Staufen1: an emerging regulator of oncogenesis through its various roles in key cellular events

Abstract

The double-stranded multifunctional RNA-binding protein (dsRBP) Staufen was initially discovered in insects as a regulator of mRNA localization. Later, its mammalian orthologs have been described in different organisms, including humans. Two human orthologues of Staufen, named Staufen1 (STAU1) and Staufen2 (STAU2), share some structural and functional similarities. However, given their different spatio-temporal expression patterns, each of these orthologues plays distinct roles in cells. In the current review, we focus on the role of STAU1 in cell functions and cancer development. Since its discovery, STAU1 has mostly been studied for its involvement in various aspects of RNA metabolism. Given the pivotal role of RNA metabolism within cells, recent studies have explored the mechanistic impact of STAU1 in a wide variety of cell functions ranging from cell growth to cell death, as well as in various disease states. In particular, there has been increasing attention on the role of STAU1 in neuromuscular disorders, neurodegeneration, and cancer. Here, we provide an overview of the current knowledge on the role of STAU1 in RNA metabolism and cell functions. We also highlight the link between STAU1-mediated control of cellular functions and cancer development, progression, and treatment. Hence, our review emphasizes the potential of STAU1 as a novel biomarker and therapeutic target for cancer diagnosis and treatment, respectively.

Phosphomimicry on STAU1 Serine 20 Impairs STAU1 Posttranscriptional Functions and Induces Apoptosis in Human Transformed Cells

“…STAU1 55 is well characterized for its involvement in cell decision during development, cell differentiation, or proliferation, through pluripotent post-transcriptional activities [13,29]. We now show that the posttranslational modification on serine 20 in the N-terminal region of STAU1 55 is sufficient to impair cell proliferation and trigger the apoptosis of cancer cells.…”

“…It also acts as an IRES-transacting factor in capindependent translation [25]. Through these molecular mechanisms, STAU1 55 regulates several physiological pathways linked to cell decision such as differentiation, proliferation, migration, apoptosis, autophagy, and stress response autophagy (reviewed in [13,19,[26][27][28][29]). In cancer cells, the proto-oncogene non-receptor tyrosine kinase SRC phosphorylates STAU1 55 on tyrosines 380 and 493 [30].…”

“…STAU1 55 expression is essential for the proliferation of non-transformed cells, as it facilitates the cell cycle checkpoint transition via a coordinated control of pro/anti-proliferative and pro/anti-apoptotic regulons [31]. Not surprisingly then, large scale comparative studies of tumor and normal tissues indicate that the STAU1 55 expression level is upregulated in most cancers, favoring the pro-proliferative (reviewed in [13,29]) and malignant [32,33] phenotypes. It was suggested that STAU1 55 could be considered as an oncogene and that the high level of STAU1 55 could indeed be a potential biomarker for prostate cancer [34], high grade gliomas [35,36], and stage IA and IB lung squamous cell carcinoma [37].…”

RNA-binding protein signaling in adult neurogenesis

“…LCN2 is an alternative pathway for the delivery and uptake of physiological iron (Qu et al, 2020). The role of LCN2 in cell iron transport and homeostasis has recently been investigated (Devireddy et al, 2005;Bao et al, 2010). The LCN2 gene encodes an iron-binding protein that has been shown to regulate the density and morphology of hippocampal dendritic spines in the brain (Mucha et al, 2011).…”

“…Stau1 and Stau2 are involved in RNA transport as well as mRNA stability and translation (Almasi and Jasmin, 2021). The Stau1 gene encodes the Stau1 protein (Bondy-Chorney et al, 2016).…”