RBM39, also known as RNA binding motif protein 39, is a protein found within human cells that plays a broad role in cellular activities. It has garnered significant scientific attention due to its diverse involvement in various biological processes. Understanding RBM39’s functions helps illuminate how cells operate and how disruptions in these functions can impact health. Researchers are striving to uncover its precise mechanisms and implications for disease.
Understanding RBM39
RBM39 is a protein characterized by its ability to bind to RNA molecules, which are involved in carrying genetic information and facilitating protein production. This protein contains several RNA recognition motifs (RRMs) and a U2AF homology motif (UHM), which enable its interactions with RNA and other proteins.
RBM39 is primarily located in the nucleus of cells, where it co-localizes with core spliceosomal proteins. Its presence in this location underscores its involvement in the complex processes that occur within the nucleus, particularly those related to gene expression.
RBM39’s Role in Gene Expression
A primary function of RBM39 is its involvement in RNA splicing. After DNA is transcribed into pre-messenger RNA (pre-mRNA), splicing removes non-coding regions, called introns, and joins the coding regions, known as exons, to form mature messenger RNA (mRNA). This precise editing process ensures that functional proteins are created from the cell’s genetic instructions. RBM39 promotes the inclusion of specific exons through its regulation of exon cassette splicing.
RBM39’s role extends to regulating gene expression, influencing which proteins are produced, when, and in what quantities. It can act as a coactivator for certain transcription factors, including steroid nuclear receptors like estrogen receptors and JUN/AP-1, independently of its splicing factor activity. RBM39 also binds to its own pre-mRNA, regulating the inclusion of a “poison exon” that can lead to the degradation of its own mRNA, a form of autoregulation.
RBM39 and Human Health
Dysregulation or mutations in RBM39 can contribute to various human health conditions, particularly certain types of cancer. RBM39 has been identified as a factor in the growth of various malignancies, including breast, colorectal, acute myeloid leukemia (AML), and gastric cancers. In some contexts, RBM39 can promote tumor growth, while its depletion can inhibit cell cycle progression and lead to tumor regression in preclinical models.
For instance, in osteosarcoma, a type of bone cancer, RBM39 has been shown to be overexpressed and its inhibition suppresses tumor growth. In colorectal cancer, elevated RBM39 levels are linked to worse survival rates, with studies indicating it enhances cancer cell proliferation, migration, and invasion, while inhibiting apoptosis.
Beyond cancer, emerging research is exploring RBM39’s involvement in neurodegenerative disorders. While RBM39 itself is not directly implicated in neurodegenerative conditions in the same way as its close relative RBM3, the broader family of RNA-binding proteins, including RBM3, is recognized for their roles in neurological health. Understanding the general functions of RNA-binding proteins in maintaining proper nervous system function provides context for future research into RBM39’s potential indirect or direct roles in these complex diseases.
RBM39 in Scientific Research
Scientists are actively studying RBM39 to understand its precise mechanisms and its potential as a therapeutic target. Researchers are investigating how RBM39 interacts with other cellular components and the intricate ways it regulates gene expression and RNA splicing.
A significant area of research focuses on RBM39 as a target for drug discovery, particularly in cancer treatment. Certain aryl sulfonamide drugs, such as indisulam, have been found to act as “molecular glues” that promote the degradation of RBM39, leading to aberrant splicing events and tumor regression in preclinical models. These findings highlight a promising avenue for developing therapies that modulate RBM39 activity to combat various diseases, including solid tumors and leukemias.