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One of my favorite parts of my job is the teaching that I get to do every year around this time. One of Oxford’s many charming idiosyncracies is the tutorial system they use for undergraduate teaching. In addition to lectures and labs, each student gets one-on-one or small group tutorials in their fields of study. Every Hillary Term (January – March) I get a number of first year undergraduates to drill on genetics. It’s a great way for them to learn (and for me to teach) – kind of the Socratic method in action – and often really good fun. Oxford is one of the best universities in the world and often I get to teach undergraduates that are incredibly bright and push me to think while teaching. This kind of intellectual challenge keeps things fresh even if I am teaching the same things every year.

And that is generally the case as the first three tuts that I do are pretty standard – gene expression, Mendelian genetics and practical molecular genetics – but the fourth is kind of a wild card. I try to cover some “sexy” science topic that they may see more of as they progress along their academic careers. For the past couple of terms I’ve focused on epigenetics – chromatin and RNA regulation of gene expression. Just in case I needed affirmation that I had picked a good topic, this week’s Nature was chock full of RNA-based epigenetics papers.

RNA is a funny little molecule. Most people, if they think of it at all, think of RNA as the intermediate between DNA and protein – kind of a cellular bicycle messenger. But in reality, RNA is a powerful and volatile agent in the cell. In addition to playing important roles in protein translation and splicing there are numerous classes of non-coding RNA that act as potent modifiers of the expression of genes. This runs in contrast to the central dogma of molecular biology which states that DNA serves as a template to make RNA which serves as a template to make proteins – the fundamental building blocks of life.

The first of a trio of hot new papers this week looks at an example of examples of noncoding RNA acting on DNA to suppress breast cancer metastasis. There are species of very small RNAs, known as microRNAs (miRNA), that are used to regulate gene expression by altering transcription of DNA. These miRNA are very important in normal human growth and development and represent another way in which the expression of genes is regulated. Expression of a number of these miRNAs are lost in metastatic breast cancer cells. A group led by Joan Massague at the Sloan-Kettering Cancer Center in New York reported in Nature that expression of two of these microRNAs (miR-126 and miR-335) is sufficient to reduce tumor growth and proliferation and to inhibit metastatic cell invasion. In other words, reactivating a pair of small noncoding RNAs in cancer cells is capable of contolling the spread of cancer. These results open the door to exciting new treatment possibilities, unfortunately still hindered by the lack of an effective delivery system.

More news on the cancer and RNA front comes out of a joint effort by Hengmi Cui and Andrew Feinberg’s groups at Johns Hopkins University. In this week’s Nature they publish results demonstrating that a human tumor suppressor is inactivated by RNA in cancer cells. Normally, tumor suppressors prevent cancer cell formation by regulating cell proliferation. In cancer cells, tumor suppressor genes are often silenced (turned off) allowing for the runaway growth of these cells. Many of these TSGs are found near genes coding for antisense RNAs, a class of small RNA similar to microRNAs that can control expression of related genes. One such TSG, p15, appears to be silenced in vitro by a p15 antisense RNA. It’s important to note that these experiments are all done in vitro and it is a fairly big jump to the assumption that the same thing happens in human cancers. The results are interesting nonetheless and these two papers reveal some of the complexity of cancer biology – noncoding RNA plays roles to both suppress cancer metastasis and to allow cancer cell proliferation.

The last of the Nature RNA trio is my personal favorite. In some ciliates – tiny water protozoans – most of the germ line DNA, prior to transmission to progeny, is chopped up into hundreds of thousands of fragments. These pieces are unscrambled and reassembled in the progeny to allow for normal gene expression in the somatic nuclei. A group at Princeton University led by Laura Landweber demonstrate that one such ciliate makes a complete RNA copy of the DNA genome to serve as a template for rearrangement and reassembly of the germ line DNA. What’s exciting about this result is its implications in the evolution of life. It has long been postulated that the first life on earth used an RNA “genome”. This paper is the first description of RNA serving as a heritable genetic template, in other words containing the necessary genetic information for subsequent generations.

Image Credits:

All of the images from today’s post are RNA inspired paintings by Julie Newdoll.