Controlling Protein Diversity

"A major question in biology today is how human cells with 30,000 genes produce at least 120,000 proteins," said Dr. Bert O'Malley, chair of the BCM department of molecular and cellular biology. The answer is a process called alternative splicing in which certain information from a gene is left out or included, changing the format of the resulting protein.

In other words, if the information in a gene is like the elements of a computer code, leaving out some of the code results in a very different program than what would have resulted if all the components had been included or different parts had been left out. In this instance, leaving out part of the gene changes the protein.

"The question is, 'How is this controlled?'" said O'Malley.

He and his colleagues have shown in previous studies that hormones like estrogen and progesterone can change the amounts of proteins made by their target genes. When hormone binds to receptors inside the cells, they are activated to seek out target genes. They then recruit the coactivators – in this case CAPERá and CAPERâ. These coactivators not only cause the gene to begin the process that results in protein production, they also determine what kind of RNA (a kind of genetic template for the protein) is made as well as what kind of protein results.

"This subgroup of coactivators, when brought to the gene, can enhance the amount of RNA made off the gene or the quantitative expression of that gene as well as qualitatively change what comes off the gene in terms of what protein is made," said O'Malley. These coactivators are unusual in that they can both control alternative splicing that results in different proteins being made as well as the production of RNA.

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Others who participated in the research include Drs. Susan M. Berget, Dennis H. Dowhan, Eugene P. Hong, Didier Auboeuf, Andrew P. Dennis and Michelle M. Wilson of the BCM departments of molecular and cellular biology and biochemistry and molecular biology. This research was supported by grants from the National Institutes of Health, the National Institutes of Child Health and Human Development, the National Institute of Diabetes, Digestive and Kidney Diseases and the Welch Foundation.