The Negative Elongation Factor Complex Member E (NELF-E), also known as RD RNA Binding Protein or RDBP, is a crucial component of the Negative Elongation Factor (NELF) complex. This complex plays a significant role in the regulation of transcription elongation by RNA polymerase II. The NELF complex consists of four subunits: NELF-A, NELF-B, NELF-C/NELF-D, and NELF-E .
NELF-E is a protein coding gene that encodes a polypeptide chain containing 403 amino acids with a molecular mass of approximately 45.6 kDa . The recombinant form of NELF-E is often produced in Escherichia coli (E. coli) and is fused to a 23 amino acid His-Tag at the N-terminus to facilitate purification .
The primary function of the NELF complex, including NELF-E, is to negatively regulate the elongation phase of transcription by RNA polymerase II. This regulation is achieved through the induction of transcriptional pausing approximately 20-60 nucleotides downstream from the transcription start site . NELF-E provides the strongest RNA binding activity within the NELF complex and is essential for recruiting the complex to RNA .
The NELF complex works in conjunction with the DSIF (DRB-sensitivity inducing factor) complex to inhibit the progression of RNA polymerase II during transcription elongation . This pausing mechanism is counteracted by the P-TEFb (positive transcription elongation factor b) kinase complex, which phosphorylates components of the NELF and DSIF complexes, leading to the release of the paused polymerase and resumption of transcription .
The regulation of transcription elongation by the NELF complex is crucial for proper gene expression and cellular function. In addition to its role in normal cellular processes, the NELF complex has been implicated in the regulation of HIV-1 latency. The complex is involved in the formation of the HIV elongation complex in the absence of the HIV Tat protein, contributing to the maintenance of viral latency .
Mutations or dysregulation of the NELF-E gene have been associated with various diseases, including femoral vein thrombophlebitis and familial apolipoprotein C-II deficiency . Understanding the function and regulation of NELF-E is essential for developing therapeutic strategies for these conditions.