Penn Medicine News Blog

October 24, 2014 // By Karen Kreeger // Comments

Roundabout RNA: How Circular RNAs Form

Basic Science // Research // Translational Research

Wilusz Genes Dev blog post pic from Science. jpgThe body's main molecular currency is most definitely proteins but less than 2 percent of the DNA in the human genome codes directly for them. So just what does that other 98 percent do? That’s where RNA comes in.

RNA is both the bridge between DNA and proteins and the toolbox that helps proteins do their everyday work. RNA exists in a variety of forms, each with a particular role and purpose, not all of which are fully understood. Penn scientists are at the forefront of exploring and pushing back the boundaries of the bewilderingly complex world of RNA. And, Jeremy Wilusz, PhD, a new faculty member in the department of Biochemistry & Biophysics, is adding to that knowledge with a recently published paper in Genes & Development on circular RNAs.

Until recently, only a handful of these curious RNAs were known to be found in nature in such things as virus particles called viroids and in hepatitis delta virus, which causes human liver disease. Genomic sequencing, however, has now revealed the presence of thousands of circular RNAs in organisms ranging from archaea to humans. For example, human fibroblasts alone have more than 25,000 circular RNAs, notes Wilusz in an earlier commentary in Science.

“Over the last few years, it has become increasingly clear that many protein-coding genes purposely don’t make protein-coding mRNAs (and eventually working proteins), but instead make circular non-coding RNAs,” says Wilusz. “This observation is completely against the central dogma of molecular biology. We were very intrigued by this and aimed to figure out the mechanism that determines why some genes make circles, while others do not.” The G&D paper describes how a cell "decides" to make these circular RNAs.

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