C-sis internal ribosome entry site (IRES)

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RF00549

C-sis internal ribosome entry site (IRES) refers to a specific RNA sequence found within the 5' untranslated region (5' UTR) of the PDGF-B (platelet-derived growth factor B) chain gene, known as c-sis. This IRES plays a crucial role in the translation process of the PDGF-B gene under certain cellular conditions, particularly when cap-dependent translation initiation is inhibited or less efficient. The presence of IRES elements allows for the alternative initiation of protein synthesis, ensuring the production of essential proteins during stress conditions, such as hypoxia or apoptosis.

Function

The primary function of the C-sis IRES is to mediate the internal initiation of translation of the PDGF-B chain mRNA. This is particularly important in conditions where the general cap-dependent translation is compromised. IRES elements like the C-sis IRES enable the cell to selectively translate proteins that are critical for cell survival, stress response, and adaptation. The PDGF-B protein, translated from mRNA containing the C-sis IRES, plays a significant role in cell growth, proliferation, and the healing process by acting as a potent mitogen for cells of mesenchymal origin.

Structure

The structure of IRES elements, including the C-sis IRES, is complex and involves secondary and sometimes tertiary RNA structures that can recruit the ribosome directly to the mRNA, bypassing the need for the traditional cap-binding proteins. These structures are recognized by specific IRES trans-acting factors (ITAFs) that facilitate the binding of the ribosomal subunits to the RNA, allowing translation initiation to occur internally rather than at the 5' end of the mRNA.

Biological Significance

The C-sis IRES has significant implications in cell biology and molecular biology, particularly in the context of cancer and wound healing. The ability to initiate translation via an IRES mechanism allows cells to rapidly respond to environmental stresses by synthesizing proteins necessary for survival and adaptation. In the context of cancer, the upregulation of IRES-mediated translation can contribute to tumor growth and survival by ensuring the continuous production of growth factors, like PDGF-B, even under conditions that would normally inhibit protein synthesis.

Research and Clinical Implications

Understanding the mechanisms governing IRES-mediated translation, and specifically the role of the C-sis IRES in PDGF-B synthesis, has potential therapeutic implications. Targeting the IRES elements or their interaction with ITAFs could provide a novel approach to controlling the expression of proteins involved in disease processes, including cancer and fibrotic diseases. Additionally, manipulating IRES activity could offer strategies for enhancing the expression of beneficial proteins in therapeutic contexts, such as tissue regeneration and repair.