The Identification And Functional Evaluation Of Small, Non Coding RNAs In The Regulation Of Complex Biological Processes

ORLANDO, FL () - In a joint meeting of the SBUR and SUO, Dr. Victoria Robinson discussed that small non-coding RNAs are important in the regulation of complex biological processes. She stated that RNA was probably the first biological molecule, have lots of secondary structure and catalyze reactions and serve critical functions. Only 2% of our DNA codes for protein and the other 85% was felt to be "junk". Yet, now it is felt that half of that is unique DNA and the majority of the human genome is transcribed into RNA. Non-coding RNAs (ncRNAs) are a large family of molecules and very diverse. The ncRNAs are powerful sequence specific post-transcriptional regulators for gene expression. One siRNA targets one miRNA. miRNA are endogenously encoded genes with diverse physiological functions. They bind target mRNAs and suppress translation. In contrast to siRNA, miRNA targets many mRNAs. While siRNA forms intracellular complexes, miRNA are transcribed into hairpin loops that is then unwound and each piece can target different genes.


The first miRNA was described in 1933 and the second one in 2000. In 2001, 3 papers showed that miRNA was conserved in many organisms, including humans. In situ hybridization of miRNA was described in 2007 and now it is a blooming field of research. The name given to miRNA reflects the species and sequence and order of discovery. miRNA is now recognized to be endogenous genes and are an ancient mechanism of gene regulation. There are >700 human miRNAs presently described. Target algorithms predict hundreds of targets for each miRNA. In one study, algorithms to predict the number of targets is variable, thus target validation is required.


miRNAs are tumor suppressor genes and can undergo mutation. For example, p53 undergoes transcriptional activation and miR-34 is expressed and involved in regulation of this pathway. Challenges in the field include better target prediction and databases. Cancer cells in general may use an alternative splicing mechanism to avoid miR regulation. Also, mammalian protein translation is not fully understood and understanding other ncRNA mechanisms such as heterochromatin silencing is under investigation. She concluded that every tumor type has mRNAs and will be developed as tumor targets.


Presented by Victoria Robinson, MD, at the Annual Meeting of the American Urological Association (AUA) - May 17 - 22, 2008. Orange County Convention Center - Orlando, Florida, USA.


Reported by Contributing Editor Christopher P. Evans, MD, FACS


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