Novel Mechanism for Control of Gene Expression

Researchers at Boston University have discovered a novel, evolutionarily conserved mechanism for the regulation of gene expression. The new work by Dr. David Levin and Dr. Ki-Young Kim is reported in the March 4, 2011 issue of Cell. Normal cell growth, embryonic development, and responses to stress, require proper spatial and temporal control of gene expression. Studies on control of transcription (RNA biosynthesis) are typically centered on understanding how the RNA polymerase is recruited to the promoter, the control region of a gene. However, the new work has revealed the existence of a second level of control in a yeast model system. The researchers found that genes expressed solely under certain stress conditions are normally maintained in a silent state by a process called transcriptional attenuation. In attenuation, the RNA polymerase initiates transcription of the gene, but its progress is terminated prematurely by a termination complex that binds to the polymerase. Attenuation occurs commonly in bacteria, but was not previously known to operate in eukaryotic cells (those with a nucleus). “In response to an inducing stress signal, attenuation must be overcome so that a target gene can be expressed,” said Dr. Levin. “The way that works in this instance is that an activating transcription factor, called Mpk1, serves double duty—it is first responsible for recruitment of the RNA polymerase to the promoter, but Mpk1 then binds to the transcribing polymerase to block association of the termination complex.” Mutations in a human protein, called Senataxin, which is related to a component of the yeast termination complex, are responsible for causing juvenile-onset forms of ALS and ataxia, two neuromuscular degenerative diseases. In their new research, Dr. Levin and Dr.