Dr. David Levin, Professor of Molecular¹ & Cell Biology at Boston University Henry M. Goldman School of Dental Medicine and Professor of Microbiology at Boston University School of Medicine discovered recently a novel, evolutionarily conserved² mechanism³ for the regulation of gene⁴ expression. The study describing this work titled, "Mpk1 MAPK Association with the Paf1 Complex Blocks Sen1-Mediated Premature⁵ Transcription Termination," appears in the March 4 issue of Cell. Normal cell growth, embryonic⁶（胚胎的） development, and responses to stress, require proper spatial⁷（空间的） and temporal（暂时的） 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, new work from Levin and postdoctoral fellow, Ki-Young Kim, has revealed the existence of a second level of control in a yeast⁸ model system.

They found that genes⁹ expressed solely¹⁰ under certain stress conditions are normally maintained in a silent state by a process called transcriptional attenuation¹¹（衰减）　. In attenuation, the RNA polymerase initiates¹² transcription of the gene, but its progress is terminated prematurely¹³ by a termination complex that binds¹⁴ to the polymerase. Attenuation occurs commonly in bacteria, but was not previously¹⁵ known to operate in eukaryotic（真核的） 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 Levin. "The way that works in this instance is that an activating¹⁶ 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 transcribing¹⁷ polymerase to block association of the termination complex."

Mutations in a human protein, called Senataxin, which is related to a component¹⁸ of the yeast termination complex, are responsible for causing juvenile-onset forms of ALS and ataxia（运动失调）　, two neuromuscular degenerative diseases.

In their newest research, Levin and Kim show that the discovered attenuation mechanism is evolutionarily conserved in humans. "The findings of this research have broad implications that translate to human cells," said Levin. "We know that when the key yeast proteins are replaced by their human counterparts, they are able to engage in the same interactions to exert（运用，发挥） control over attenuation."

Levin believes that attenuation is actually a widespread phenomenon. "Approximately 10% of yeast genes appear to be under attenuation control, which suggests that it may also be common in humans," said Levin. "This opens the door to the possibility of new approaches to therapeutic¹⁹ gene silencing, now that we know transcriptional attenuation operates in eukaryotic cells and that it's a regulated process."