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8.10:

Transcription Elongation Factors

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Molecular Biology
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JoVE Core Molecular Biology
Transcription Elongation Factors

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Once transcription is initiated in the cell, the initial transcription factors are released from the pre-initiation complex.  The RNA polymerase must then add new nucleotides to the 3′ end of the growing RNA strand in a phase called transcription elongation.  Elongation in eukaryotes is challenging, as the DNA in a non-dividing cell exists as a condensed network called the chromatin.  In the chromatin, the DNA is tightly wound around charged histone proteins at repeated intervals. These DNA–histone complexes are called nucleosomes. When the RNA polymerase encounters the nucleosomes, or other DNA binding proteins, or some specific DNA sequences, it may halt. The inability to translocate further may lead to dissociation of the RNA polymerase before the complete gene is transcribed.  To avoid this, the cell recruits special accessory proteins that can help the RNA polymerase execute an uninterrupted elongation process on the gene.  The eukaryotic elongation factors associate directly with RNA polymerase and help it move smoothly along the template DNA strand and carry out its catalytic activity.  In addition, the cell also recruits some other proteins, such as ATP-dependent chromatin remodelling complex and histone chaperones, which allow the transcription machinery to access the condensed genomic DNA inside the chromatin. These multi-subunit complexes disrupt the interaction between the histone core and the DNA resulting in the restructuring or repositioning of the nucleosomes.  Alteration in the nucleosome architecture helps create nucleosome-free regions of the DNA that can be easily accessed by the transcription machinery.  Once the pre-mRNA is synthesized, the histones must be reinstated on the DNA template. The chromatin remodelling proteins and the histone chaperones thereafter, rewind the DNA around the histone proteins, completing the nucleosome reassembly process.

8.10:

Transcription Elongation Factors

Transcription elongation is a dynamic process that alters depending upon the sequence heterogeneity of the DNA being transcribed. Hence, it is not surprising that the elongation complex's composition also varies along the way while transcribing a gene.

The transcription elongation is regulated via pausing of RNA polymerase on several occasions during transcription. In bacteria, these halts are necessary because the transcription of DNA into mRNA is coupled to the translation of that mRNA into a protein. However, in eukaryotes, the transcription is coupled with mRNA processing. Hence, pausing of RNA polymerase around exon-intron junctions is necessary for increasing the efficiency of mRNA splicing.

These halts in RNA Polymerase activity may be reversible or irreversible. In case of a reversible pause, proteins such as TFIIF, elongins, ELL, ensure that the RNA Polymerase resumes elongation after a brief pause. However, if the halt in RNA Polymerase activity is irreversible, it becomes a transcriptional arrest. If transcription is arrested, then the enzyme cannot resume elongation on its own. In such a situation, elongation factors such as TFIIS and pTEFb enable RNA Polymerase II to read through the DNA template at transcriptional arrest sites.

In addition, ATP-dependent chromatin remodeling factors and histone chaperones are also involved in the regulation of transcription elongation. Together they can alter the positions of nucleosomes along the DNA, making it accessible or inaccessible to the transcription machinery.

Hence, RNA polymerase needs the help of several factors to cruise through chromatin and specific sequences that interfere with transcription.

Suggested Reading

  1. Sims, Robert J., Rimma Belotserkovskaya, and Danny Reinberg. "Elongation by RNA polymerase II: the short and long of it." Genes & development 18, no. 20 (2004): 2437-2468.
  2. Winston, Fred. "Control of eukaryotic transcription elongation." Genome biology 2, no. 2 (2001): reviews1006-1.