Regulation of cyclin D1 RNA stability by SNIP1

Cameron P. Bracken, Steven J. Wall, Benjamin Barré, Kostya I. Panov, Paul M. Ajuh, Neil D. Perkins

    Research output: Contribution to journalArticle

    62 Citations (Scopus)

    Abstract

    Cyclin D1 expression represents one of the key mitogen-regulated events during the G(1) phase of the cell cycle, whereas Cyclin D1 overexpression is frequently associated with human malignancy. Here, we describe a novel mechanism regulating Cyclin D1 levels. We find that SNIP1, previously identified as a regulator of Cyclin D1 expression, does not, as previously thought, primarily function as a transcriptional coactivator for this gene. Rather, SNIP1 plays a critical role in cotranscriptional or posttranscriptional Cyclin D1 mRNA stability. Moreover, we show that the majority of nucleoplasmic SNIP1 is present within a previously undescribed complex containing SkIP, THRAP3, BCLAF1, and Pinin, all proteins with reported roles in RNA processing and transcriptional regulation. We find that this complex, which we have termed the SNIP1/SkIP-associated RNA-processing complex, is coordinately recruited to both the 3' end of the Cyclin D1 gene and Cyclin D1 RNA. Significantly, SNIP1 is required for the further recruitment of the RNA processing factor U2AF65 to both the Cyclin D1 gene and RNA. This study shows a novel mechanism regulating Cyclin D1 expression and offers new insight into the role of SNIP1 and associated proteins as regulators of proliferation and cancer.
    Original languageEnglish
    Pages (from-to)7621-8
    Number of pages8
    JournalCancer Research
    Volume68
    Issue number18
    DOIs
    Publication statusPublished - 15 Sep 2008

    Keywords

    • Bone Neoplasms
    • Cell Cycle
    • Cell Line, Tumor
    • Cyclin D1
    • Gene Expression Regulation, Neoplastic
    • HeLa Cells
    • Humans
    • Intracellular Signaling Peptides and Proteins
    • Nuclear Proteins
    • Osteosarcoma
    • Polymerase Chain Reaction
    • RNA, Messenger
    • RNA, Neoplasm
    • RNA, Small Interfering
    • Ribonucleoproteins
    • Transcription, Genetic
    • Transfection

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  • Cite this

    Bracken, C. P., Wall, S. J., Barré, B., Panov, K. I., Ajuh, P. M., & Perkins, N. D. (2008). Regulation of cyclin D1 RNA stability by SNIP1. Cancer Research, 68(18), 7621-8. https://doi.org/10.1158/0008-5472.CAN-08-1217