RNA: More Than Just a Messenger

RNA biology is a central area of research at Wistar, where scientists are working to further our understanding of the functions of RNA and their relevance to cancer, infections and other types of diseases.

While most people know about DNA and its function as the material that carries our genetic information, fewer people are familiar with its distant cousin RNA. However, RNA has been known since the late 1800s, and research on its function has been recognized with some 30 Nobel Prizes over the years.

The central dogma of biology, formulated in the 20th century after the discovery of DNA, postulates that genes provide instructions for the cell to build proteins, or functional molecules needed to perform the different jobs in the cell, and that RNA serves as an intermediate messenger to transmit the flow of genetic information from DNA to its encoded protein products. This process involves two main steps: transcription and translation. In the first step, the DNA sequence of a gene is “copied” in a similar pattern to make an RNA molecule called messenger RNA (mRNA). In the second step, the sequence of the mRNA is translated into a combination of amino acids to build the protein product, and this process requires a switch to a different “language” (from nucleic acid to amino acids), hence the name translation.

But is this the whole story?

While this still holds true, we now know that RNA is much more than just a messenger, and scientists have started to appreciate the complexity and versatility of functions of the different RNA populations.

The vast majority of the mammalian genome is transcribed to RNA, yet less than three percent of it encodes for proteins. So, what is the function of all those other RNA molecules that don’t get translated into proteins?

Scientists have found that the majority of the RNA transcripts play regulatory roles in gene expression and genome architecture, controlling when and how the genetic information is expressed and adding a whole new level of complexity to our understanding of life.

The term noncoding RNA (ncRNA) includes a variety of RNA species that do not act as messengers for protein production but carry out equally important functions. The first to be discovered, in the late 1950s, were the ribosomal RNA (rRNA) and transfer RNA (tRNA), both involved in the process of protein synthesis. Biology students have learned about these RNAs on their textbooks for decades.

In the 1980s RNA editing was discovered as the process through which cells can make discrete changes in the sequence of nucleotides — the “letters” in the RNA code, ultimately generating diversity in the protein products.

Wistar science played a leading role in this discovery when Kazuko Nishikura, Ph.D., who currently serves as professor in the Gene Expression and Regulation Program, characterized a family of enzymes called ADAR (adenosine deaminase acting on RNA) that are responsible for RNA editing.

Since 2000, the field of RNA biology has been in the midst of a renaissance thanks to the discovery of several new classes of noncoding RNAs and their functions have profound implications for basic biology as well as medicine. The first to be studied were small noncoding RNAs. These small RNA molecules with bizarre names – siRNA, miRNA and piRNA – are short regulatory RNA species that silence gene expression by inducing the degradation of messenger RNA or by interfering with protein production. Small RNAs have gained huge popularity as molecular biology tools to study the function of target proteins in the laboratory. Additionally, they have been investigated as novel classes of therapeutic agents for a range of disorders including cancer and infections.

Long noncoding RNAs (lncRNA) are the youngest addition to the noncoding RNA family. Their function can influence several steps involved in gene expression, resulting in either silencing or promoting it. Since 1996, when the first to lncRNA was discovered, thousands of scientific papers have been published on lncRNAs, and they have rapidly risen to a major field of investigation for their role in cell physiology and disease. A significant piece of information was added to the lncRNA puzzle through research conducted at Wistar in 2010, which led to the identification of more than a thousand lncRNAs expressed in several tissues and the characterization of their role in enhancing gene expression.

In line with its tradition of pioneering work in RNA biology, Wistar’s Gene Expression and Regulation Program has a main focus on RNA-mediated gene regulation to understand its role in cancer development and as a target for novel therapeutic approaches.