- Elongin A is a transcription elongation factor that plays a key role in enhancing the rate and efficiency of RNA polymerase II (Pol II) transcription through protein-coding genes.
- It is encoded by the ELOA gene and functions as the catalytic subunit of the Elongin complex, which is composed of elongin A, elongin B, and elongin C. While elongin B and C serve primarily as adaptor and stabilizing subunits, elongin A provides the direct transcriptional activity by stimulating Pol II to overcome pausing during the elongation phase. This makes elongin A critical for maintaining high transcriptional fidelity and productivity in actively expressed genes.
- Mechanistically, elongin A enhances transcription by suppressing transient pausing of Pol II on the DNA template, thereby accelerating RNA chain elongation. This activity ensures that transcription proceeds smoothly and efficiently after initiation. The Elongin complex can interact with additional factors involved in RNA processing and chromatin remodeling, further coordinating transcription elongation with downstream RNA maturation events. In this capacity, elongin A acts as a central regulator of transcriptional output, especially in genes requiring rapid or sustained expression.
- Elongin A also participates in other molecular complexes, most notably the von Hippel–Lindau (VHL) E3 ubiquitin ligase complex, often called the VBC complex. In this context, elongin B and elongin C form a stable adaptor heterodimer that binds pVHL, cullin-2, and Rbx1 to assemble an E3 ubiquitin ligase. While elongin A itself is not a structural component of the VBC ligase, it shares evolutionary and functional relationships with elongin family proteins that contribute to ubiquitin-mediated protein degradation. The association of elongins with both transcription and protein turnover highlights their dual importance in gene regulation and proteostasis.
- Beyond its canonical role in transcription elongation, elongin A has been implicated in cellular stress responses and gene-specific regulation. For example, it can act as a transcriptional coactivator for certain signal-dependent genes, linking environmental cues to changes in transcriptional elongation. It is also thought to interact with factors involved in DNA repair and genome stability, suggesting broader roles in maintaining cellular homeostasis.
- Clinically, elongin A has not been as extensively studied as elongin B and C, which are directly involved in the VHL tumor suppressor pathway. However, emerging evidence suggests that dysregulation of elongin A expression or function may contribute to pathological conditions, including cancer. Its ability to influence transcription elongation efficiency could affect oncogene and tumor suppressor gene expression, thereby altering cell growth and survival. Furthermore, as transcription elongation is increasingly recognized as a key control point in gene regulation, elongin A is gaining attention as a potential factor in disease progression and therapy response.
