Joan Steitz: RNA is a many-splendored thing

W hen it was first discovered, RNA was thought to have just one job in the cell: that of a messenger carrying the genetic instructions for protein synthesis to the ribosomes. But, since then, different RNA species have been shown to be key to the construction (1) and function of the ribosomal machinery and to control both the spliced state and levels of messenger RNAs (2–4). Right from the start, Joan Steitz has been in the middle of this RNA revolution. An early experience as an undergraduate hooked her on research. Enthralled by RNA's elegant form and function, Steitz went on to do her graduate work with James Watson at Harvard and followed up with postdoctoral work in Cambridge, England (5). She then set up shop at Yale, continuing her groundbreaking research to discover new niches for RNA in the cell (1–4, 6). We called her to talk about the passion she has for RNA and how it's driven her career. You've been quoted as saying you " fell in love with RNA " early on in your career… I fell in love with RNA in one of my fi rst jobs as an undergraduate. I loved the idea of mRNA, which was discovered at that time. I also found the functions of other RNAs, like ribosomal RNA and transfer RNA, fascinating. And, since then, it just keeps getting better and better ; we keep fi nding out more and more of RNA's functions. RNA was a real mystery when you started working on it… When I was a graduate student at Har-vard, I was working on an RNA bacteri-ophage. We were trying to fi gure out what protein products the messenger RNA encoded. Of course we didn't have sequences—actually the genetic code had just been fi nalized—so you couldn't just look at the sequence and fi gure out what the proteins were. As a postdoc, I worked on a project trying to fi gure out how ribosomes recognize where to start translation on a messenger RNA. At that early stage it wasn't known whether the coding region would start right at the 5 Ј end and go all the way to the other end, but there were hints that it was more complicated than that. So my project was to identify the initiation codon and surrounding sequences that determine where the ribosome binds to bacterio-phage mRNA to start making …