In 1981. Courting days.
I have been
reading about these little buggers a lot lately, and I think they’re
exciting. They may help “clinicians”
decide what treatments to use in cases of advanced ovarian cancer (OC), they may
serve as early-warning signals, enabling doctors to get at the tumor before it
spreads – and they may even give us a clue as to what causes OC, possibly
facilitating prevention and/or cure.
Let’s hope.
Many of you
are far more familiar with RNA and protein synthesis than I will ever be, but
let me start with a little background.
Proteins do almost everything worth doing in our bodies. The blue-prints for the thousands of proteins
we need are encoded on our DNA molecules in the form of sequences of four
“nucleotide bases”, A (Adenine), G(Guanine), T(Thymine), and C(Cytosine). To make a protein, an RNA molecule is created
by “reading” the DNA sequence, then goes to a strange object called a Ribosome
where it is read in turn, to form a protein.
The process of transcribing the DNA blue-print onto what is known as a
messenger RNA is called “transcription”, for fairly obvious reasons. The RNA molecule – called a “messenger” RNA,
mRNA - may undergo all sorts of
complicated modifications thereafter, before arriving at at the ribosome, where
it in turn is read, leading to the construction of a protein molecule. As the “language” of proteins (strings of
amino acids) is different from that of DNA and RNA (strings of nucleotides),
this last step is called “translation”.
As anyone who has had Biology 101 will recognize, this is a gross
over-simplification.
The typical
mRNA may be many hundreds, even thousands of nucleotide bases long. Recently, a species of RNA has been
discovered that is much shorter than mRNA – average length about 22 nb. These are called microRNAs, abbreviated
miRNA. They were found first in a tiny
worm, but now are known to be in virtually everything, so long as it’s
alive. There are hundreds of them. One thing they do is to modify some mRNAs
“post-transcriptionally”. Sometimes they
even “silence” the mRNA, so that some protein or other doesn’t get built. They were discovered only a decade or so ago,
and their functions are still being investigated. They tend to be “up-regulated” in some kinds
of cancer. They can be detected and
their abundance estimated by use of blood samples. They may serve as “oncogenes”, by suppressing
generation of proteins that would signal cells to die. Heck, who knows what the little things can
and can’t do? I keep trying to learn
about them, but I tend to get stymied by sentences such as “*A similar situation
has also been described for one mammalian miRNA, mirR-196; the near perfect base paring between miR-196 and Hoxb-8 directs cleavage of Hoxb-8 both in mouse embryos and in cell culture44”. Mice, again.
Where would we be without them?
If I turn up anything exciting, I’ll post it as a comment to this blurb.
(*On a quick-read-thru I find that I can almost understand this sentence. Believe me, there are much worse.)
The title of the "Comment" is: miRNA disproves Intelligent Design
ReplyDeleteI am recovering from an hour-long group discussion of research proposals – in which I was a full, although generally quiet and uncharacteristically modest, participant. I was greatly encouraged by the extent to which I could follow most of the discussion, but overwhelmed by how much more I obviously need to learn. I may have to give up on my stated goal – the Noble Prize in medicine by the time I’m 80. Maybe 90 is more realistic. Or 190.
In my spare time – and I have lots of it – I have reading about micro RNAs and their relationship to cancer. I wrote about these little devils a few days ago, but I want to add a few sentences because I have just realized that miRNA is INCONTESTABLE PROOF THAT “INTELLIGENT DESIGN” IS HOKUM. Or, if not hokum, proof that the Designer has a peculiar sense of humor.
For instance, consider the paper “MicroRNA and ovarian cancer”, published in 2008 by Corney & Nikitin of Cornell University. This interesting and marginally comprehensible paper* describes how miRNA is born and what it does thereafter. Apparently miDNA originates in the nucleus as something called pi-mRNA, but is chewed up by a so-called “transcription complex” composed of two proteins – Drosha and Pasha - then transported out of the nucleus by another protein, aptly named Exportin-5, further brutalized in the cytoplasm by still another enzyme, Dicer by name, and then goes about its business. I say “it”, but of course there are many kinds of miRNA, each with its own “business”. The ones I am most interested in, the ones implicated in ovarian cancer, apparently bind with and deactivate miRNA strands responsible for telling cells to die (apoptosis). Cells that won’t die are … cancer.**
The point here is that there is nothing at all “intelligent” about this process. If ever I stumbled on a biological Rube Goldberg, this is it. A Designer worthy of the name would have devised a far more straightforward way to do most of the things I have been reading about. What we seem to have, instead, is a process constructed by blind, blundering chance. It is as if nature, confronting a chance to “adapt”, said “Well, hell. What should I do? Maybe if I tweak this little molecule, it will work. Otherwise, I’ll tweak this other one. Eventually I’ll get it right.”
No doubt I will inflict more miRNA on you. I have high hopes. I like them so much I may bring one home as a pet.
*Much use was made of Wikipedia. Be warned.
** And this is the bare-bones treatment.
More on miRNA.
ReplyDeleteThis comment concerns a paper in Proceedings of the National Academy, by P. S. Mitchell – with 19 co-authors! – published in 2008. (No wonder bio-docs rack up such impressive publication lists!). The title of the paper is “Circulating miroRNAs as stable blood-based markers for cancer detection.” It is a good paper and understandable for the most part, although they do drop the occasional biochemical bomb: e.g., “…used 5’ and 3’ RNA-RNA linker ligations followed by RT-PCR amplification to generate a small RNA-cDNA library.” Thankfully, you don’t have to understand this kind of stuff to get at the gist of the article, which can be summarized as below:
1) miRNA is “disregulated” in epithelial cancer.
2) miRNA is found in blood plasma and serum
3) It seems to be stable there, meaning that it is not chopped up by RNase (an enzyme that chops up RNA), nor otherwise degraded
4) Using a machine/process light-heartedly named Taqman one can measure the abundance of specific miRNAs in the blood swiftly and accurately.
5) They next apply this technique to a human cancer, specifically prostate. A specific miRNA (miR-141) was found to be significantly more abundant in cases of epithelial, metastatic prostate cancer than in the control group.
6) Thus, miR-141 is a promising candidate for useful biomarker in prostate cancer. As it is somehow associated with the epithelium, it may be useful in cases of other types of epithelial cancer as well.
7) Closer scrutiny of this little sucker may even shed some light on why/how these cancers occur in the first place.
There is a lot more of interest in this article, but this is enough for now. I am going down for a second cup of coffee, and then I will try to figure out what in heck they mean when they write about “TaqMan qRT-PCR assays .”
And even more of interest on miRNA, courtesy of Carolyn Joyce:
ReplyDeletehttps://www.yahoo.com/tech/s/major-cancer-breakthrough-doctors-solve-long-standing-mystery-223029508.html
Awhile back I wrote about microRNAs, which seemed to me to represent a promising new weapon against OVCA. Well, it turns out I was right. Researchers at M. D. Anderson Cancer Center at the University of Texas have given reason to believe that miRNA551b may be such a weapon. This little <28 base-pair chunk of RNA may serve as both an indicator of OVCA as well as a means to a cure. See this slightly difficult article:
ReplyDeletehttp://www.eurekalert.org/pub_releases/2016-05/uotm-spt050516.php