Follow-up on earlier article on RNA defect repair

Last Thursday I published information on some recent Kennedy’s Disease research that looked promising even though it had not been verified by another lab.  The article, “Scientists identify compound that can help repair toxic RNA defect,” was interesting even though I didn’t understand most of it.

I asked Ed, our resident biology professor, to review the study and comment on it when he had a chance.  Below are Ed’s comments.

It is a different approach overstates the case with regard to treatment of the various CAG repeat diseases.

As you may remember, it is generally thought that the symptoms of Kennedy’s Disease (KD) (and other CAG diseases) is due to a misfolded protein and that the cells no longer have the ability to remove these proteins and this somehow causes cells to die.  This paper is based on a different proposed mechanism for cell death.  The problem is not the protein but the mRNA.  To make a protein, one needs the instructions on the order of amino acids for that particular protein.  Just like a dictionary tells you the order of letters in a word, DNA (our genes) tells you the order of amino acids in any protein.  To make a protein, one therefore needs these instructions.  Cells get the instructions by looking up the instructions for a protein (as you would look up a word in the dictionary) and makes a copy of the needed instructions.  This copy is made out of RNA is known as m (or messenger)RNA (see * below).  The experiments in this paper are based on the notion that it is actually the mRNA that is somehow causing the cell death and not the resultant protein.  The idea is the mutant mRNA binds to a protein called MBNL-1 and it is the sequestering of this protein that ultimately leads to cell death.  They found a way to prevent the mutant mRNA to bind to MBNL-1 and thus, if this is indeed the reason for cell death, block cell death.  BTW, they did not show that this chemical stops cell death just the mRNA-protein interaction.  Since it is not generally accepted that the mRNA is at fault in KD, it really is a stretch to call this a breakthrough (or even an advancement) that will lead to a treatment.

This is a difficult paper for nonscientists to discuss as the suppositions are not generally accepted and they really did not show any cell saving affects - yet the site you forwarded seems to indicate a major breakthrough.  As you may know by now, I am not a fan of such publicity as it leads to unfulfilled and unrealistic hope.  The work may end up being very important but we are a long way from it being helpful to us and that is certainly not clear in this press release.

(*) From Wikipedia:  Messenger RNA (mRNA) is a molecule of RNA that encodes a chemical "blueprint" for a protein product.  mRNA is transcribed from a DNA template, and carries coding information to the sites of protein synthesis: the ribosomes. Here, the nucleic acid polymer is translated into a polymer of amino acids: a protein. In mRNA as in DNA, genetic information is encoded in the sequence of nucleotides arranged into codons consisting of three bases each. Each codon encodes for a specific amino acid, except the stop codons, which terminate protein synthesis. This process requires two other types of RNA: Transfer RNA (tRNA) mediates recognition of the codon and provides the corresponding amino acid, whereas ribosomal RNA (rRNA) is the central component of the ribosome's protein-manufacturing machinery.