Tuesday, June 25, 2013

FAQ: Why does transcription occur primarily in the direction of genes?

Surface model of RNA polymerase II from yeast, chains colored uniquely
DNA transcription occurs when RNA polymerase binds to unwound DNA at a promoter. RNA polymerase can bind to either strand of DNA and can therefore proceed in the sense direction (toward the gene) or anti-sense direction (away from the gene). However, productive elongation occurs primarily in the gene coding direction in mammalian species. An article published in a recent issue of Nature provides some insight into why gene coding elongation is preferred.

In an article entitled: 'Promoter directionality is controlled by U1 snRNP and polyadenylation signals' the authors from MIT describe two processes that confer the bias toward gene coding elongation. The authors propose that the asymmetric presence of polyadenylation sites and U1 small nuclear ribonucleoprotein binding sites is at the heart of this phenomenon.

The role of polyadenylation sites in the cessation of transcription and aid in nuclear export of mRNA transcribed from genes is well characterized. These polyadenylation sites also appear to be abundant in regions in the anti-sense direction proximal to a promoter. This leads to the early cessation of transcription in this direction.

In contrast U1 small nuclear ribonuculeoprotein binding sites are more abundant in the sense direction proximal to the promoter. This protects the elongating mRNA from early termination and cleavage. The corresponding paucity of binding sites in the antisense direction combined with the early cessation associated with increased polyadenylation sites leads to short RNA's produced in this direction which are rapidly cleaved.

This situation is clearly preferential from a standpoint of energy consumption; production of long non-coding RNA's would be an unnecessary burden. This is especially relevant when you consider the fact that only about 15 percent of the genome encodes for protein-coding genes.