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Sunday, March 25, 2007

RNA Polymerase Genes in the Human Genome

 
The structure of yeast RNA polymerase II was solved by Roger Kornberg [Nobel Laureate: Roger Kornberg]. There are many different polypeptide subunits labelled Rpb1 to Rpb12 in the nomenclature used by yeast workers. The mammalian enzyme is very similar. Most of the same subunits are present but they have different names.

The core of RNA polymerase is composed of two very large subunits called Rpb1 and Rpb2 in yeast. In mammals they are called subunits A (220 KDa) and B (140 KDa). These subunits are homologous to the β and β′ subunits in bacterial RNA polymerases. The genes for these polypeptides in humans are called POLR2A and POLR2B. They are located on chromosomes 17p13.1 and 4q12 respectively.

The Online Mendelian Inheritance in Man database has entries for both genes but there are no genetic diseases associated with mutations in either gene [OMIM POLR2A and OMIM POLR2B]. This should not be a surprise since it is rare for genetic diseases to be associated with important essential genes.

Recall that mammals have four different RNA polymerases [Eukaryotic RNA Polymerases]. Both RNA polymerase I and RNA polymerase III have homologous large A and B subunits. The genes for these polypeptides are called POLR1A (194 KDa, chromosome 2p11.2), POLR1B (128 KDa, chromosome 2q13), POLR3A (155 KDa, chromosome 10q22-q23), and POLR3B (~120 KDa, chromosome 12q23.3). As is the case with the large subunits of RNA polymerase II, none of these genes are associated with metabolic diseases because they are essential, important housekeeping genes.

These genes make up a typical eukaryotic gene family. It's important to remember that a gene family refers to homologous genes within the same genome and not to a group of homologous genes from different species. Gene families arise from gene duplication events.

The "A" genes evolved from a common ancestral RNA polymerase β gene several billion years ago and the "B" genes evolved from an ancestral β′ gene. The β and β′ genes, in turn, evolved from a common ancestor near the time life began about 3.5 billion years ago.

The "A" and "B" genes have evolved independently by divergence. In such cases the family members are often on different chromosomes and the intron-exon organization of each member is very different in spite of the fact that the genes are still closely related in amino acid sequence.

In addition to the "A" and "B" genes for each RNA polymerase, there are genes for three different subunits of RNA polymerase I (POL1C, POL1D, POL1E), 12 different subunits of RNA polymerase II (SURB7 and POL2C - POL2L), and 9 different subunits of RNA polymerase III. There are also dozens of genes for the general transcription factors required for initiation, elongation, and termination. Altogether, there are at least 80 different genes required for transcription and that's not counting any gene-specific regulatory genes.

The fourth RNA polymerase in humans is the mitochondrial version. Its gene is POLRMT located on chromosome 19p13.3. The large subunit of the mitochondrial RNA polymerase is only distantly related to the others. There are no metabolic defects associated with mutations in POLRMT [OMIM POLRMT].

1 comment :

Anonymous said...

To add a bit on your entry, a splice variant of PolIV has been shown to be made and the PolIV protein was localized to the nucleus.