If the picture of complexity regarding how genes are controlled and regulated in the genome was not complicated enough, a new study has increased this paradigm to an unprecedented level.1 Recently reported research describes massively long gene tails that do not code for proteins, but instead contain hundreds to thousands of built in regulatory switches per gene RNA copy.
When a protein-coding gene is turned on in the genome, copies of it are made called mRNAs. These mRNAs are then processed to remove non-protein coding intervening regions called "introns" and also to join together the protein coding regions called "exons." Most genes in the human genome undergo a highly complex and regulated process called "alternative splicing" that produces mRNA gene copies with different sets of exons. As a result, a single gene has the capability to produce many different types of mRNAs that code for a wide array of proteins.2,3
This recent study in both mice and humans now shows that not only are the exons of a gene alternatively spliced, but so is the sequence that is tagged onto the end of a gene called the "3-prime untranslated region" (3' UTR)—like a "tail" at the end.1 This 3' UTR tail does not code for protein, but instead contains a variety of genetic switches that allow the gene to be regulated after it is copied or transcribed.
The 3' UTR gene tails contain a variety of regulatory features. Some of them allow regulatory RNA-binding proteins to attach to the mRNA's tail while others allow small regulatory RNAs—called micro RNAs—to bind. The combination of these bound regulatory molecules fine-tunes and robustly controls genes after the mRNAs are produced. This is a form of regulation called "post-transcriptional," meaning after the mRNA is transcribed.
Like the protein-coding areas of the gene, these 3' UTR tails are also alternatively spliced and thus variable. Their size and makeup can vary widely and dynamically between mRNAs from the same gene and between the different cell types in which they are found.
While scientists knew that the 3' UTRs of genes had this capability several years ago, they recently discovered that this feature was on a scale much more intricate and massive than they anticipated. In this study, they identified 2035 mouse and 1847 human genes that have 3' UTR tails ranging from 500 to 25,000 bases long. In some cases, they were even longer than the protein-coding areas of the genes themselves. These incredibly long gene tails literally contain hundreds to thousands of genetic switches within each single mRNA.
The complexity of genetic control at this level astounds researchers—each network of genes related to a certain cell process is composed of hundreds to thousands of individual genes, each with this type of intricate regulatory set of features. Not only that, but genetic networks in the cell also overlap and function together dynamically, continually, and robustly as part of normal cell physiology.
The level of coordination of such genetic complexity is almost beyond human comprehension and clearly the product of incredible bioengineering from an Omnipotent and Wise Creator.
- Miura, P., et al. 2013. Widespread and extensive lengthening of 3′ UTRs in the mammalian brain. Genome Research, Published online March 21, 2013 in advance of the print journal. doi:10.1101/gr.146886.112
- Barash, Y., et al. 2010. Deciphering the splicing code. Nature. 465 (7294): 53-59.
- For a brief review of alternative splicing, see: Tomkins, J. 2012. The Irreducibly Complex Genome: Designed from the Beginning. Acts & Facts. 41 (3): 6.
*Dr. Tomkins is Research Associate at the Institute for Creation Research and received his Ph.D. in Genetics from Clemson University.