Staufen1 localizes to the mitotic spindle and controls the localization of RNA populations to the spindle

Abstract

Staufen1 (STAU1) is an RNA-binding protein involved in the post-transcriptional regulation of mRNAs. We report that a large fraction of STAU1 localizes to the mitotic spindle in colorectal cancer HCT116 cells and in non-transformed hTERT-RPE1 cells. Spindle-associated STAU1 partly co-localizes with ribosomes and active sites of translation. We mapped the molecular determinant required for STAU1–spindle association within the first 88 N-terminal amino acids, a domain that is not required for RNA binding. Interestingly, transcriptomic analysis of purified mitotic spindles revealed that 1054 mRNAs and the precursor ribosomal RNA (pre-rRNA), as well as the long non-coding RNAs and small nucleolar RNAs involved in ribonucleoprotein assembly and processing, are enriched on spindles compared with cell extracts. STAU1 knockout causes displacement of the pre-rRNA and of 154 mRNAs coding for proteins involved in actin cytoskeleton organization and cell growth, highlighting a role for STAU1 in mRNA trafficking to spindle. These data demonstrate that STAU1 controls the localization of subpopulations of RNAs during mitosis and suggests a novel role of STAU1 in pre-rRNA maintenance during mitosis, ribogenesis and/or nucleoli reassembly.

Distinct roles for the RNA-binding protein Staufen1 in prostate cancer

“…Currently, there is a paucity of information on the impact of Staufen1 in cancer biology [37,50,[52][53][54][55][56][57][58]. Yet, its implication in several key RNA processes in a variety of cell types indicates that it likely plays pivotal roles in cancerous cells.…”

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

“…HEK 293T (ATCC, CRL-11268) and HeLa cells (ATCC) were grown in Dulbecco's modified Eagle's medium (DMEM; #SH30022, HyClone, GE Healthcare Life Sciences, Logan, UT, USA) containing 10% fetal bovine serum (#SH30910, Hyclone, GE Healthcare Life Sciences), 1% penicillin-streptomycin (1000 U/ml) (#SV30010, Hyclone, GE Healthcare Life Sciences), and 1% amphotericin B (25 mg/ml) (#SV30078.01, Hyclone, GE Healthcare Life Sciences), at 37ºC in a 5% CO 2 atmosphere. SKO, Staufen1 knockout cells were generated from parental HCT116 cells as previously described ( 36 , 60 ), and both cell lines were maintained in McCoy's Media (#16600082 Life Technologies, Thermo Fisher Scientific Inc.) supplemented with 1% penicillin/streptomycin and 10% fetal bovine serum (Hyclone).…”

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

“…Moreover, in HCT116 cells, STAU1 has been shown to affect cell growth by controlling localization of a group of pre-rRNAs during mitosis. This may play critical roles in the assembly of ribosomes and protein translation [ 8 ].…”

“…In the past two decades, a growing body of literature has explored the role of STAU1 in RNA localization [7,8], splicing [9,10], stability [11,12], translation [13,14], and decay [15][16][17]. Findings from such studies led to additional investigations into the mechanistic roles of STAU1 in a variety of cell functions.…”