Research provides new insights into role of mechanical forces in gene expression

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Research provides new insights into role of mechanical forces in gene expression
Human BiologyNervous SystemBiotechnology
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The genome inside each of our cells is modelled by tension and torsion -- due in part to the activity of proteins that compact, loop, wrap and untwist DNA -- but scientists know little about how those forces affect the transcription of genes.

Transcription of a gene begins when RNAP binds to a 'promoter' DNA sequence and ends at a 'terminator' sequence where the mRNA copy is released. The canonical view of termination holds that after releasing the mRNA, RNAP dissociates from the DNA. A team of researchers has demonstrated how force plays a role in an alternative to canonical termination.

RNA polymerase is a type of protein that produces mRNA. It tracks processively along double helical DNA, untwists it to read the base pair sequence of only one strand and synthesizes a matching mRNA. Such"transcription" of a gene begins when RNAP binds to a"promoter" DNA sequence and ends at a"terminator" sequence where the mRNA copy is released. The canonical view of termination holds that after releasing the mRNA, RNAP dissociates from the DNA.

Furthermore, they found that the ability of a sliding RNAP requires the C-terminal domain of the alpha subunit to recognize a promoter oriented opposite to the direction of sliding. These subunits"allow it to stay on track, flip around and grab the other strand of the DNA double helix where another promoter might be," she said. Indeed, with the alpha subunits deleted, flipping around to oppositely oriented promoters did not occur.

"My hope is that one day we will have a spatio-temporal map of forces acting on the genome at various times during the life cycle of various types of cells in our organism. Our research highlighting the effect of forces on the probability of repetitive transcription may then help predicting and plotting, in a heat map sort of way, the different levels of transcription of different genes," Finzi said.

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