mRNA Not Equal in All Cells

Scientists identify a false assumption of standard gene expression analyses that could lead to the reappraisal of many prior studies.

By | October 26, 2012

Wikimedia, GuillomThe common belief that cells have similar total amounts of messenger RNA (mRNA)—a notion that underpins researchers’ interpretations of global gene expression analyses—is not true, according to a report out this week (October 25) in Cell. Gene expression analysis is now one of the most commonly used methods in biology, and the findings could call into question the interpretation of a broad range of published studies.

Researchers led by Richard Young at the Whitehead Institute for Biological Research in Cambridge, Massachusetts, found that aggressive cancer cells produce several times more RNA than other cells. Moreover, three different commonly used methods for gene expression analysis—DNA microarrays, RNA sequencing, and digital molecular barcoding—masked these differences.

“We then realized that the common assumption that cells contain similar levels of mRNA is badly flawed and can lead to serious misinterpretations,” Jakob Lovén, a postdoc in Young’s lab, said in a press release. Thus, expression data being used to gain insights into cancer cell behavior and regulation should be interpreted with caution.

Indeed, the study may lead biologists to reappraise old research that relied on gene expression analysis, if that proves possible, said David Orlando, another scientist in the Young lab. “There are over 750,000 expression datasets in public databases, and because they generally lack information about the cell numbers used in the analysis, it is unclear whether they can be re-examined in order to validate the original interpretation,” he said in the press release. “It may be necessary to reinvestigate some important concepts.”

The team does, however, suggest a solution for future gene expression studies: use synthetically produced mRNAs—known as RNA spike-ins—as standardized controls to compare with experimental data and to eliminate erroneous assumptions about total RNA.

Add a Comment

Avatar of: You



Sign In with your LabX Media Group Passport to leave a comment

Not a member? Register Now!

LabX Media Group Passport Logo


Avatar of: James V. Kohl

James V. Kohl

Posts: 492

October 26, 2012

The content of some specialty publications suggests it is the balance of microRNA to mRNA that controls intracellular signaling homeostasis and stochastic gene expression. I hope that someone will address the contribution of nutrient chemicals on the microRNA side of the divide -- if indeed it is a divide that should be explored further in the context of adaptive evolution.

Avatar of: mlerman


Posts: 71

October 26, 2012

 The only correct way to measure gene expression is measure the number of mRNA molecules per cell (not per DNA, or rRNA, or tissue/cell wet weight) any other approach is incorrect and totally misleading. Somebody has to analyze this myriad (~1 million of deposits) critically before the data bases will become operational, otherwise an enormous avalanche of mistakes and misconceptions will flood the field/literature. Michael Lerman, M.D.,Ph.D.

Avatar of: Dr Ichha Purak

Dr Ichha Purak

Posts: 17

October 27, 2012

As formation of mRNA is related with gene  expression through translation process producing required enzymes for special metabolic processes or pathways. So mRNA amount is generally propotional to the need of cell for proteins or enzymes or its gene expression. Cancer cells exhibit unconrolled cell cycle and other alterations so mRNA production is greatly affected

Avatar of: Mounthell


Posts: 52

October 28, 2012

Both "normal" and cancerous cells are "controlled" by the cell's micro-environmental regime.  When it changes, the translation ensemble changes as it is subsequently induced.  All cellular "control" results from its regimes' historical spatiotemporal trajectory.

Thus, _net_ mRNA reflects the state at that particular cellular location at that time.  (So-called "oncogenes" are simply normal DNA sequences transcribed in a peculiar micro-environmental regime leading to the effects we recognize as being carcinogenic.)

Avatar of: EmpireWorker


Posts: 3

November 22, 2012


Twitter / Dewyvantol: Wikimedia, GuillomThe common belief that cells have similar total amounts of messenger RNA (mRNA)—a notion that underpins empirework researchers

Popular Now

  1. Secret Eugenics Conference Uncovered at University College London
  2. Like Humans, Walruses and Bats Cuddle Infants on Their Left Sides
  3. How Do Infant Immune Systems Learn to Tolerate Gut Bacteria?
  4. Scientists Continue to Use Outdated Methods