核糖核酸聚合酶在基因转录过程中的作用

In all organisms, RNA synthesis is carried out by proteins – known as RNA polymerases（聚合酶） (RNAPs) – that transcribe¹ the genetic³ information from DNA⁴ in a highly-regulated, multi-stage process. RNAP is the key enzyme⁵ involved in creating an equivalent RNA copy of a sequence of DNA. This transcription is the first step leading to gene² expression. While the major steps in RNA synthesis have been known for several decades, scientists have only recently begun to decipher（解释） the detailed⁶ molecular⁷ steps of the complex transcription process. In research published in the July 1, 2010 online Early Edition of the Proceedings⁸ of the National Academy of Sciences, University of Maryland biophysicists Devarajan (Dave) Thirumalai and Jie Chen, along with Rockefeller University collaborator⁹ Seth Darst, provide new insight into how the transcription process is initiated¹⁰ and the role that RNA polymerase plays in making this happen. Because the sequence, structure, and function of multi-subunit RNA polymerase are universally conserved¹¹（保存，保全） in all organisms -- from bacteria to humans -- understanding the mechanisms¹² of bacterial¹³ gene transcription is an important step in deciphering（破译，解释） the role of genetics in disease.

"Previously¹⁴, people didn't know the precise role of RNA polymerase in initiating¹⁵ transcription," explains Distinguished¹⁶ University Professor Dave Thirumalai (Department of Chemistry and Biochemistry and Institute for Physical Science and Technology), "but we showed that it plays an important role in forming the transcription bubble and in the process of bending the DNA to facilitate entry of DNA into the active site. That is the process we described computationally."

Their simulation of the initiation¹⁷ phase of transcription in bacterial RNA polymerase showed a three-step process. It begins when the RNA polymerase binds¹⁸ with transcription promoting regions of DNA. Through interactions with the RNA polymerase, the DNA helix then unwinds, forming an open "bubble" that allows the polymerase access to the exposed DNA sequence to begin transcription. The DNA molecule¹⁹ then bends to relieve stress produced by the opening.

Dr. Jie Chen, who conducted this research while a graduate student in the Chemical Physics program, simulated the transcription bubble formation using a Brownian dynamics²⁰-based computer model developed by Dr. Thirumalai's laboratory. "By creating this molecular movie, we can look at the dynamics（动力学） of RNAP and simulate how it shifts from one structure to another structure," explains Chen. "Our simulation confirms experimental observations, and goes further to establish a clear and active role for RNA polymerase."

Dr. Thirumalai's research group is continuing to study RNA polymerase by looking at the second phase of the transcription process in bacteria and also through models of human transcription.