Before the lecture, ASBMB president Dr. Steven McKnight opened the meeting with a moment of silence in memory of members who had passed away during the past year. He then announced that the society is in good financial shape with a strong organization and great organizational morale. He also called upon attendees who were not members of ASBMB to consider joining the society. I was particularly glad to hear him call upon attendees to take time to visit posters by trainees at the meeting. I agree with him that when a well-known scientist visits your poster it can be really exciting. I remember going to the 1998 Yeast meeting and talking to Robert Simpson, who was one of the people I had read extensively on yeast chromatin remodeling. The fact that he took the time to talk with me meant so much. Finally, Dr. McKnight honored past president Jeremy Berg (who I met today and I tried not to geek out to much but I’m not sure I kept it together).
Okay, confession: I am a nucleic acid structure geek. In my biochemistry class I focus on DNA and RNA tertiary structure. I get a little crazy when people draw mRNA as a straight line. I knew I was in for a treat with Dr. Joan Steitz talking about non-coding RNA. In setting up the context of her research, Dr. Steitz asked a basic question: how do non-coding RNAs help the virus? If viral genomes are small and limited, the non-coding RNA must be pretty important. Additionally, if viruses are constantly exchanging DNA with the host cell, are they getting the DNA for some of these non-coding RNA from the host? If so, what function are they carrying out in the host? And don’t assume that they carry out the same function in the virus- they’re pretty good at co-opting and using them for a different purpose.
Hosts organisms (like humans) do have non-coding DNA, and the amount of non-coding DNA increases with organismal complexity, reaching 98.5% in humans. What do the non-coding RNA produced by this DNA do? In many different ways they are involved in regulating gene expression in conjunction with proteins.
There is a long history of non-coding RNAs being known about in herpesviruses. As Dr, Steitz pointed out, the technology has finally caught up to the science to ask the interesting questions about the functions of these non-coding RNA. One particular viral non-coding RNA found in the Kaposi’s Sarcoma Herpes Virus is expressed at high levels in infected cells during the lytic phase. The question is how the RNA is able to accumulate to over 500,000 copies per cell?
Here’s the cool part- it stabilizes itself through formation of a triple helix between a motif called ENE and the poly-A tail. Triple helical RNA! How great is that! It forms Watson-Crick and Hoogsteen base pairs. What made it complicated to understand is that it is not just a stretch of poly-U, but every 6 bases there is a break in the sequence. I’m not going to go into the details of how they determined it, but the break was required because as the triple helix formed hydrogen bonds they got too close together and sterics impinged on the ability to form additional bonds.
One of the other things that I loved about the talk was the way that Dr. Steitz was able to relate the very cool biochemistry to the bigger clinical question of herpesviruses and in particular how these non-coding RNAs might result in oncogenic transformation linked to the viruses since a lytic cycle precedes the onset of tumorigenesis.