O mestre da célula

quarta-feira, março 31, 2010

The Scientist

Volume 24 | Issue 4 | Page 42
Date: 2010-04-01

By Judy Lieberman

Master of the Cell

RNA interference, with its powerful promise of therapy for many diseases, may also act as a master regulator of most—if not all—cellular processes.



RNA silencing. Computer artwork showing a length of RNA (yellow with red rings) bound to an RNA-induced silencing complex (RISC).
© Medi-Mation Ltd / Photo Researchers, Inc.


One of the biggest surprises in biology in the past decades was the discovery that humans have about the same number of protein coding genes as a worm. That puzzling finding began to make sense when we realized that we were missing a big part of the picture: a lot of DNA is transcribed into RNA but never into proteins. The more we learn about these RNAs, the more we realize how much complexity they add. Some of these noncoding RNAs, called microRNAs because of their small size, interfere with protein expression by chopping up protein coding transcripts or inhibiting their translation into proteins. Their effect on cell fate and function is far wider than we initially thought. In recent years, it has become clear that microRNAs can act as master switches by regulating large networks of genes.

I came to work on microRNAs by a circuitous path. I started as a theoretical high-energy particle physicist, but after 8 years decided to go to medical school to do work that more directly helped people. As part of my medical training in hematology and oncology, I began a postdoc at MIT in the lab of Herman Eisen in the early eighties when molecular biology was just coming into its own: The T-cell receptor had just been discovered (work to which the Eisen lab contributed), and HIV was about to be identified as the cause of AIDS. With no therapy available then, AIDS patients died a truly gruesome death. The Eisen lab studied the cytotoxic T cells that were supposed to protect us against viral infections like HIV.

After my postdoc, I was offered a job at Tufts–New England Medical Center that combined clinical work in hematology with running a lab. I decided that my new lab would work on understanding the T-cell response to HIV and why these cells fail to control the infection, with an eye towards developing immune-based therapy. We also investigated how cytotoxic T cells activate programmed cell death (apoptosis) in virally infected cells.

I was immersed in HIV and T-cell immunology work in 1998 when I read the Fire and Mello paper1describing one of the first examples of RNA interference (RNAi) inC. elegans. I was intrigued and perplexed by the paper: how could a double-stranded RNA possibly silence gene expression? I would periodically ask a colleague working on worms, Keith Blackwell, if there was an explanation for this strange phenomenon.
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