non-coding and microRNAs

You mentioned the intricacies of the genome. I have heard the the term non-coding RNA. How does that fit into the scheme of the genome?

Thank you for the topic suggestion!

In the 1990s a new player took the stage in scientific research, microRNAs. This new player has changed the focus of how genes are regulated in the cell.

Previously, the major players in the cell were proteins. They are the functional unit and workers in the cell. For example, the protein called BRCA1 (breast cancer 1 protein) is involved in DNA repair when the DNA is damaged. It is also mutated in some people and that mutation is linked to the development of some forms of breast cancer.

Proteins are made by translation of a RNA molecule, remains in the cell for a defined period of time (depending on the specific protein) and is degraded by other protein-dependent mechanisms of various sorts. The RNA in the cell functioned to translate the code from DNA to the protein. Some specialized RNAs, messenger RNA, transfer RNA and ribosomal RNA, exist to help in this process.

That was prior to the 1990s and the recognition of non-coding RNAs, especially microRNA (aka miRNAs). Non-coding RNAs are RNA molecules that have a role in the cell, but do not create proteins to carry out that function. This includes the RNAs mentioned above (transfer, messenger and ribosomal) and also includes a newly identified class of RNAs that have very important roles in the cell, the small non-coding RNAs. This class now contains microRNAs, small interfering RNAs, and Piwi-associated RNAs. For today, the focus will be microRNAs.

MicroRNAs are short stretches of RNA nucleotides (the A,C,U,G bases) that are only 20-30 bases in length. It’s short (transfer RNAs, messenger RNAs can be 100-1000s of nucleotides long)! These miRNA are very important for controlling protein expression levels and do so by controlling the translation step from messenger RNA to protein. (For example, the BRCA1 gene is encoded in the DNA on Chromosome 17. When it is expressed the DNA is transcribed and a BRCA1 messenger RNA is created. This messenger RNA is then translated by transfer and ribosomal RNA and other proteins into the actual BRCA1 protein).

MicroRNAs control protein expression in a variety of ways - they bind to the messenger RNA and degrade it so there is no RNA template available to create the protein - or they bind to the messenger RNA and prevent the message from being translated into the protein by disrupting the translation machinery without altering the messenger RNA amount itself. In either case, the overall amount of the protein product is reduced and this can have dramatic consequences on the cell.

The real advantage of microRNAs is speed. They can rapidly control the level of protein in a cell, much faster than if a protein has to be made from turning on the transcription of the DNA, then creating the messenger RNA, then creating the protein. Alternatively, it can rapidly remove a protein from a cell by binding to the messenger RNA and essentially silencing it. Need more protein? Remove the microRNA bound to the messenger RNA and more protein will be translated! Have too much and need to eliminate protein quickly? Bind a microRNA to the messenger RNA and prevent protein translation.

This area of research has exploded! Since they were discovered, over 400 different microRNAs have been identified. They control expression of many proteins and are critically important in the cell. Many microRNAs have been shown to be altered in cancers (either too much or too little) suggesting that a problem (and therefore a potential therapeutic target) could be that microRNA expression is out of whack.

This discovery will change how scientists think about control of protein expression. Control of protein expression is no longer a linear process.

Just entering microRNA into the PubMed scientific literature search engine yields almost 8500 papers on the topic already! I think in the future we’ll see use of microRNAs and these other small non-coding RNAs as therapy to treat disease.