Dr. Andy

Reflections on medicine and biology among other things

Wednesday, July 13, 2005

Small nuclear RNAs and cancer

The central dogma of molecular genetics is that DNA codes for RNA which codes for protein which does the work. Like many dogmas this one captures an essential truth, but is incomplete. It has become clear over the last 25 years or so that RNA can have functional roles beyond just coding for protein. For example, essential components of the ribosome, which translates RNA into protein are composed of RNA.

Now, a whole new class of RNAs has emerged:
During the past few years, molecular biologists have been stunned by the discovery of hundreds of genes that encode small RNA molecules1. These microRNAs (miRNAs) — 21 to 25 nucleotides in length — are negative regulators of gene expression. The mechanisms by which they work are similar in plants and animals, implying that they are involved in fundamental cellular processes.
These miRNAs bind to mRNAs (m is for messenger here) which encode proteins and prevent/decrease their translation, thereby decreasing the amount of protein produced. They can also target the mRNAs they bind for destruction, preventing production of any protein at all.

Now, three papers in the June 6th Nature (quote above from commentary by Meltzer) implicate these miRNAs in cancer. One paper shows that similar cancers express similar patterns of miRNAs and that the tissue of origin could generally be determined from miRNA expresison, even for very poorly differentiated tumors (those that don’t look much like any normal tissue). This was not true for expression of mRNAs encoding protein. This could actually be a practical approach to patients presenting with tumors so poorly differentiated that no one is sure what kind of cancer they are (a not so uncommon problem) and therefore how best to treat them. In addition, the first article showed that miRNAs are expressed at lower levels in tumors than in normal tissue

Another paper solves the mystery of why certain cancers, B cell lymphomas, often contain an extra copy of a piece of chromosome 13. It turns out this region encodes miRNAs that when overexpressed lead to faster cell growth (this is different than the first paper which showed in general decreased expression of miRNAs in cancer). Overexpression of these miRNAs in a mouse model of lymphoma hastened tumor development. Finally, a third paper demonstrates that c-myc, a gene known to be involved in a variety of cancers (i.e. an oncogene) affects expression of miRNAs including those identified in the second paper as important in lymphoma development.

Together the papers introduce a new level of complexity into the regulation of cell growth and division, and the perturbations in these processes that underlie cancer and remind us that things are always more complex than they first seem


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