Arginine methylation of ubiquitin‐associated protein 2‐like is required for the accurate distribution of chromosomes

Abstract

Proper bioriented attachment of microtubules and kinetochores is essential for the precise distribution of duplicated chromosomes to each daughter cell. An aberrant kinetochore-microtubule attachment results in chromosome instability, which leads to cellular transformation or apoptosis. In this article, we show that ubiquitin-associated protein 2-like (UBAP2L) is necessary for correct kinetochore-microtubule attachment. Depletion of UBAP2L inhibited chromosome alignment in metaphase and delayed progression to anaphase by activating spindle assembly checkpoint signaling. In addition, UBAP2L knockdown increased side-on attachment of kinetochores along the microtubules and suppressed stable kinetochore fiber formation. A proteomics analysis identified protein arginine methyltransferase (PRMT)1 as a direct interaction partner of UBAP2L. UBAP2L has an arginine- and glycine-rich motif called the RGG/RG or GAR motif in the N terminus. Biochemical analysis confirmed that arginine residues in the RGG/RG motif of UBAP2L were directly methylated by PRMT1. Finally, we demonstrated that the RGG/RG motif of UBAP2L is essential for the proper alignment of chromosomes in metaphase for the accurate distribution of chromosomes. Our results show a possible role for arginine methylation in UBAP2L for the progression of mitosis.

UBAP2Lis amplified in a large subset of human lung adenocarcinoma and is critical for epithelial lung cell identity and tumor metastasis

“…In Drosophila, the UBAP2L ortholog has been shown to associate with the RNA-binding protein FMR1 (2). We (unpublished data) and others have confirmed this interaction by mass spectrometry experiments in human cells (8). UBAP2L has also been identified as an RNA-binding protein in human cell lines and mouse embryonic stem cells (19).…”

“…Studies have shown that the depletion of UBAP2L suppresses migration and proliferation of prostate cancer cells and inhibits growth of human glioma and colorectal carcinoma cells (5)(6)(7). Recently, it has been shown that the arginine methylation of UBAP2L by protein arginine N-methyltransferase 1 is required for the proper distribution of chromosomes during mitosis (8). Moreover, we have shown that UBAP2L interacts with the Polycomb group protein B lymphoma Mo-MLV insertion region 1 homolog (BMI1), a well-known determinant of hematopoietic stem cell function.…”

UBAP2L arginine methylation by PRMT1 modulates stress granule assembly

“…In vitro methylation was conducted following combined instructions as described previously [20,31]. Briefly, HA-PRMT1 was purified from HEK293 cells using a protein G Sepharose column, and then reacted with 1 μl of recombinant UBAP2L (Origene, Beijing, China), 80 μM S-adenosylmethionine (NEB, Beijing, China), and 1 × PBS in a reaction volume of 30 μl.…”

“…Numerous studies indicated its association with various types of cancer [25][26][27][28][29][30]. It is required for the accurate distribution of chromosomes during mitosis [31]. A recent study suggested that it is involved in SG formation [32]; however, the cellular and molecular mechanisms underlying the role of UBAP2L in the regulation of SG assembly and disassembly need to be further investigated.…”

Downregulation of UBAP2L Inhibits the Epithelial-Mesenchymal Transition via SNAIL1 Regulation in Hepatocellular Carcinoma Cells

“…UBAP2L interacts with the polycomb complex protein B lymphoma Moloney murine leukemia virus insertion region 1 (BMI1) to maintain hematopoietic stem cell activity [17] and plays an important role in the progression of mitosis by correcting kinetochore-microtubule attachment [18]. BMI1 is a well-known polycomb group (PcG) protein that has been reported to be associated with the EMT of cancer cells [19].…”