Insights into the detailed structure of the RNA polymerase I enzyme have been provided by Fernandez-Tornero et al.and Engel et al. The discovery's significance lies in the fact that RNA polymerase I, shortly called Pol I is responsible for the synthesis of ribosomal RNA which in turn is inevitably required protein production. Pol I is thus essential for cell survival, growth, as well as proliferation. Any enzyme malfunction can therefore cause cell death or uninhibited proliferation as in cancer cells.
RNA polymerases are transcriptional enzymes facilitating the transcribing of DNA to RNA by controlling the movement of a DNA template along their active site. In eukaryotes, there are several types of RNA Polymerases each of which is specialized for unique RNA production. Pol I is the most significant among the RNA Polymerases.
The functional difference of Polymerases is mainly due to the subunit complexes which influence the ability of the enzyme to transcribe specific genes. The complete 14 subunit yeast Pol I structure revealed key structural features associated with its specific function of transcription of ribosomal RNAs.
A Zinc- Carbon domain is present at the carboxy terminus of A12.2 subunit of Pol I which gets inserted into the active site of the enzyme. This domain is essential for removing faulty RNA sequences to enhance transcription efficiency. The subunit is highly stable compared to its counterparts in Pol II and Pol III. The stability in turn is attributed to the presence and interaction of the Zinc-Carbon domain with the dimerization domain.
The study has revealed the contact points and types of interactions which offer stability for the subcomplex. Transcription by Pol I enzyme is facilitated by a closed clamp like structure which moves along the DNA template sequence which is to be transcribed. Crystallographic studies revealed the structure of the A43 -A 14 subunit complex which forms this closed clamp and thereby contributing to the higher efficiency of Pol I. The parallel functional subcomplexes in Pol II and Pol III are transient in nature.
The crystal structure isolated was found to be a dimer in which stalk of one unit gets inserted into the DNA binding cleft of the other. The dimers also showed a wide cleft facilitating its anchoring of RNA-DNA template. The Pol I crystal isolated by Femandez and colleagues exhibited varying degree of cleft widening. This has been found to be relative differences in pivoting of two modules 'core' and 'shelf' which in turn is due to the presence of large subunits A 135 and A 190 near the active site.
Engel's study focussed on inhibited bacterial Pol I enzyme which revealed similar pivoting and cleft widening variations. Further studies are needed to understand the process of formation of pre initiation complex, mechanism of elongation and termination of transcription along the DNA template. Such a study would require the detailed structural variations of Pol I enzyme when bound to regulators of transcription especially with reference to the cleft widening.
However, this study has been an important step in revealing the exact nature of transcription of general eukaryotic polymerases especially Pol I. Further revelations can help scientists to search for transcriptional factor based cure for genetic diseases such as cancer.
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1. Fernandez-Tornero, C. et al. Nature 502, 644-649 (2013).
3. Engel, C., Sainsbury, S., Cheung, A. C., Kostrewa, D. & Cramer, P. Nature 502, 650-655 (2013).
3. JOOST ZOMERDIJKl, Pivotal findings for a transcription machine, Nature 502, 629 (2013)