2017/09/03

A Few Years Ago Junk-DNA - Today, One of the Most Powerful Regulatory Mechanisms

Long non coding RNA molecules don't support Darwinian ideas of mutations and selection


Excerpt: "An individual’s risk of developing a common disease typically depends on an interaction of genetic and environmental factors. Epigenetic research is uncovering novel ways through which environmental factors such as diet, air pollution, and chemical exposure can affect our genes. DNA methylation and histone modifications are the most commonly studied epigenetic mechanisms. The role of long non-coding RNAs (lncRNAs) in epigenetic processes has been more recently highlighted. LncRNAs are defined as transcribed RNA molecules greater than 200 nucleotides in length with little or no protein-coding capability. While few functional lncRNAs have been well characterized to date, they have been demonstrated to control gene regulation at every level, including transcriptional gene silencing via regulation of the chromatin structure and DNA methylation.
 
  • LncRNAs can bind to DNA, RNA, and proteins and act in diverse ways within the cell. LncRNAs regulate gene expression by multiple mechanisms. They can guide chromatin remodeling complexes to the correct chromosomal locations controlling the balance between transcriptionally active euchromatin and silent heterochromatin both locally and globally (a).
  • Furthermore, lncRNAs can inhibit or facilitate the recruitment of RNA pol II, transcription factors, and/or cofactors to gene promoters, thereby controlling transcription of target genes (b).
  • They can regulate alternative splicing of pre-mRNAs and thereby contribute to the transcriptome complexity (c).
  • Moreover, they can affect the stability and translation of mRNA by base pairing with mRNA molecules (d).
  • LncRNAs can compete for miRNA binding and thereby preventing their function and influencing the expression of miRNA target gene expression (e).
  • They can also be processed into small, single-, or double-stranded RNAs that act as siRNAs and target other RNAs, which subsequently could result in target degradation (f).
  • Their flexible scaffold nature enables lncRNAs to join multiple protein factors that would not interact or functionally cooperate if they only relied on protein–protein interactions (g).
  • The scaffold function is also important for protein activity and localization as well as subcellular structures (h, i).
(Adapted from: Gutschner T, Diederichs S: The hallmarks of cancer: a long non-coding RNA point of view. RNA Biol. 2012 Jun;9(6):703–19)"

Here's an example of a long non coding RNA molecule. Look at its structure.
 

http://www.lncrnablog.com/the-diversity-of-long-noncoding-rnas-and-their-generation/

"These lncRNAs can be processed by several mechanisms, including ribonuclease P (RNase P) cleavage to generate mature 3′ ends, capping by small nucleolar RNA (snoRNA)–protein (snoRNP) complexes at their ends, or the formation of circular structures."

My comment: LncRNAs have several crucial roles in regulating cellular processes. Mutations in these complex structures are associated with severe diseases, such as cancer. The number of human lncRNAs in 2016 was 167,150 according to NONCODE 2016. The number of protein coding genes in human DNA is only ~19,600. Different proteins in a human body however, is up to one million.


Some lncRNAs undergo alternative splicing. Most of them regulate alternative pre-mRNA splicing. Some lncRNAs act as precursors for certain short RNA molecules, such as microRNAs.

DNA methylation is mostly regulated by lncRNAs or shorter RNA molecules derived from lncRNAs. Epigenetic markers on histones are established by maternal and paternal lncRNAs. Those markers strongly regulate skull and skeletal morphogenesis and other phenotype associated traits within organisms.

For evolutionists the significance of lncRNAs is a bad news: They are poorly conserved. The similarity between human/chimp lncRNA transcripts is only 29.8%. Human/pig lncRNA transcripts are much more similar, about 57%.

Random mutations or selection have no role in biodiversity. Everything points to Design and Creation. Don't get misled.