The Staufen1‐dependent cell cycle regulon or how a misregulated RNA‐binding protein leads to cancer

Abstract

In recent years, an increasing number of reports have linked the RNA-binding protein Staufen1 (STAU1) to the control of cell decision making. In non-transformed cells, STAU1 balances the expression of messenger RNA (mRNA) regulons that regulate differentiation and well-ordered cell division. Misregulation of STAU1 expression and/or functions changes the fragile balance in the expression of pro-and anti-proliferative and apoptotic genes and favours a novel equilibrium that supports cell proliferation and cancer development. The misregulation of STAU1 functions causes multiple coordinated modest effects in the post-transcriptional regulation of many RNA targets that code for cell cycle regulators, leading to dramatic consequences at the cellular level. The new tumorigenic equilibrium in STAU1-mediated gene regulation observed in cancer cells can be further altered by a slight increase in STAU1 expression that favours expression of pro-apoptotic genes and cell death. The STAU1-dependent cell cycle regulon is a good model to study how abnormal expression of an RNA-binding protein promotes cell growth and provides an advantageous selection of malignant cells in the first step of cancer development.

The double-stranded RNA-binding protein, Staufen1, is an IRES-transacting factor regulating HIV-1 cap-independent translation initiation

“…As previously described, Stau1 55 -HA 3 migrated at the level of Stau1 63 when resolved by electrophoresis ( 33 , 55 ). The overexpression of Stau1 55 -HA 3 has been reported to impair cell viability and proliferation ( 46 , 55 , 74 ). However, in agreement with a previous report using asynchronous HEK 293T cells ( 55 ), in the time frame of the experiment (24–48 h), the overexpression Stau1 55 -HA 3 did not impair cell viability (Figure 2G , H ) or cell proliferation (Figure 2I ).…”

“…Stau1 55 overexpression extends the G2 phase of the cell cycle ( 46 , 55 , 74 ). Also, Stau1 55 binds to the TAR stem-loop (SL) of the HIV-1 vRNA, enhancing cap-dependent translation initiation ( 33 ).…”

“…Staufen1 expression is also high in G2/M ( 55 ) and is enhanced when cap-dependent translation initiation is compromised ( 50 ). Furthermore, the expression of Staufen1 extends the G2 phase of the cell cycle ( 46 , 55 , 74 ). Therefore, it is expected that Stau1 55 is a key player and a constitutive part of the RNP-complex modulating HIV-1 IRES activity during G2/M.…”

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

“…These variations in STAU1 functions are not only limited to healthy versus diseased cells, but they are also seen in different types [ 31 , 32 , 108 ] and stages [ 76 ] of the same disease. For instance, the available evidence indicates that in several malignancies, upregulated STAU1 may act as an oncogene to manipulate normal cell functions and promote cancer development while in other cancers, STAU1 may act as a tumor suppressor and inhibit disease progression (Table 1 ).…”

High Level of Staufen1 Expression Confers Longer Recurrence Free Survival to Non-Small Cell Lung Cancer Patients by Promoting THBS1 mRNA Degradation

“…Stau1 is a double-stranded RNA-binding protein acting as a multifunctional post-transcriptional regulator [ 7 ]. Through binding to specific RNA groups, Stau1 controls their translation [ 8 , 9 , 10 , 11 , 12 ], transport and localization [ 13 , 14 ], differential splicing [ 15 , 16 ], nuclear export [ 15 , 16 ] and decay [ 17 ].…”