Nature Structural and Molecular Biology paper revealed details about how cells’ housekeeping genes are expressed.

Scientists from Albert Einstein College of Medicine report a technique that can precisely look at how a cell’s DNA gets converted to an mRNA. It marks the first time that all the individual mRNA molecules within single cells can be counted, according to the team.

The new method is a refinement of fluorescent in-situ hybridization (FISH). Until this work, FISH could only be used to look at genes or their messages that are present at very high levels and only in tissues, not at the smaller level of the cell.

One of the most important findings during the study was that housekeeping genes, which all cells need to survive, are not always expressed at a constant level. Variability, however, is restricted to a narrow range that seems to be characteristic for housekeeping genes. The team states that by combining single molecule measurement with mathematical modeling in yeast cells, they were able to precisely determine how variability is controlled.

This showed that unlike the previous findings, housekeeping genes are not transcribed by transcriptional bursts but at a fairly constant rate. Bursting expression is found for special classes for genes where higher variability might be an advantage for the cell.

The next step is to see if the continuous/non-bursting theory of housekeeping gene control applies also to human cells. The new technique will also provide a detailed look into cellular processes that until now were proven but never visualized, the researchers point out. The more detailed view of DNA being made into RNA in a single cell will help answer questions about how much of a gene is made over time and how much that level varies from cell to cell. Learning how genes work with more precision will enable investigators to understand the mechanisms that occur when genes no longer work at their correct capacity or time.

The study appeared in the November 16 online edition of Nature Structural and Molecular Biology.

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