2022/01/23

RNA-editing is the most significant reason why DNA doesn't determine organismal traits and characteristics

DNA doesn't directly predict amino acid composition of the resulting gene products


http://www.columbia.edu/cu/biology/courses/w3034/Dan/readings/RNAediting-maas.pdf

Excerpts: "It was generally believed that the DNA-encoded, exonic sequence information stored in the genome directly predicts the amino acid composition of the resulting gene products. However, this view had to be modified following the discovery of RNA editing, a process that enables a cell to recode genomic information in a systematic and regulated manner, selectively changing the readout of a gene at single nucleotide positions within the primary RNA transcript."

"...the other type of RNA editing, which is characterized by base substitution, in pre-mRNAs of higher eukaryotes. Here the open reading frame is altered, yielding a protein with one or more changes in its amino acid sequence. Substitution RNA editing was detected in many mitochondrial RNAs of higher plants with mostly cytidine-to-uridine (C-to-U) or U-to-C changes. A recent systematic analysis of Arabidopsis mitochondrial genes revealed that 8% of all containing codons are edited documenting the widespread occurrence of C-to-U editing in higher plants. Table 1 lists the different types of RNA editing and some of their characteristics. In mammals, RNA editing is mainly represented by C-to-U and adenosine-to-inosine (which functions as guanosine) (Ato-I) conversions generating single amino acid changes in the resulting protein. This often has significant consequences for protein function. Among mRNAs that were found to undergo editing, the best-characterized examples are apolipoprotein B (apoB) transcripts (C-to-U change) and messages for neuronal glutamate and serotonin receptor subunits (A-to-I changes). Since the initial discovery of mRNA editing in mammals(6,7) more than a decade ago this process of posttranscriptional modification is now recognized as an important mechanism for generating molecular diversity."

Table 1. Different forms of RNA editing


"One gene many proteins

Eukaryotic organisms use several mechanisms to increase the number of functionally different proteins produced from a single gene. This includes alternative splicing of the exons, use of different promoters, translational frameshifting or posttranslational modification. As an additional level of variation, RNA editing allows for the expression of several protein variants at the same time, depending on the number and combination of modifications introduced into individual mRNAs."

RNA editing is regulated by complex epigenetic mechanisms

https://www.cell.com/molecular-cell/pdf/S1097-2765(17)30934-6.pdf

Excerpt: "N6 -methyladenosine (m6 A) and adenosine-to-inosine (A-to-I) editing are two of the most abundant RNA modifications, both at adenosines. Yet, the interaction of these two types of adenosine modifications is largely unknown. Here we show a global A-to-I difference between m6 A-positive and m6 A-negative RNA populations. Both the presence and extent of A-to-I sites in m6 A-negative RNA transcripts suggest a negative correlation between m6 A and A-to-I. Suppression of m6 A-catalyzing enzymes results in global A-to-I RNA editing changes. Further depletion of m6 A modification increases the association of m6 A-depleted transcripts with adenosine deaminase acting on RNA (ADAR) enzymes, resulting in upregulated A-to-I editing on the same m6 A-depleted transcripts. Collectively, the effect of m6 A on A-to-I suggests a previously underappreciated interplay between two distinct and abundant RNA modifications, highlighting a complex epitranscriptomic landscape."

Summary and conclusions:
  • DNA-encoded, exonic sequence information stored in the genome doesn't directly predict the amino acid composition of the resulting gene products.
  • RNA editing is now recognized as an important mechanism for generating molecular and proteomic diversity.
  • Several epigenetic factors and mechanisms control and regulate RNA editing procedures.
  • DNA sequencing made by analyzing cDNA strands should be questioned. Most of old research investigating DNA alterations is no longer valid.
  • DNA is passive information and it has no predictive role over organismal traits and characteristics.
  • These kind of complex regulatory mechanisms point to Intelligent Design and Creation.