For by Him were all things created, that are in heaven, and that are in earth, visible and invisible,...For the invisible things of Him from the creation of the world are clearly seen, being understood by the things that are made, ...so that THEY ARE WITHOUT EXCUSE: Col 1:16 / Rom.1:20

Wednesday, March 27, 2024

RNA editing

I will praise thee; for I am fearfully and wonderfully made: 
Psalm 139:14

"When the workings of the genome were first being discovered, the central evolutionary dogma of molecular biology claimed that
genetic information passes consistently from
DNA to RNA to proteins.
Today we know that RNA messages can be altered by a variety of
mechanisms. New studies in genetics on one of these processes, RNA editing, have revealed an unprecedented level of dynamically adaptive genome complexity that defies the conventional evolutionary paradigm.

All major animal groups from jellyfish to humans use amazing cellular machinery to modify RNA that’s transcribed (copied) from both protein-coding and non-coding RNA genes.

One of the first RNA-modifying systems that researchers uncovered is alternative splicing, where a single gene can have its modular components added, removed, doubled, or even combined with the products of a completely separate gene. Thus, a single gene can produce a wide array of RNA variants, including many different protein forms if the RNAs are translated (made into proteins).

Incredible variability can be achieved through alternative splicing, but the genetic possibilities don’t stop there.
RNA editing is another form of dynamic RNA alteration.
Unlike alternative splicing that
---shuffles large chunks of DNA sequence around,
RNA editing
---targets single bases.

The most common type of RNA editing in animals involves changing an adenosine base to an inosine base (A-to-I editing).
The inosine base, which isn’t part of the standard genetic code, is interpreted as a guanine base at the ribosome where proteins are made.
This type of editing in both protein-coding and non-coding RNAs has been found to have profound effects on gene expression.
Also, the alteration of RNA transcripts coding for proteins creates yet another dynamic system of diversity in the cells’ protein complement, which is called a proteome.

The process of RNA editing appears to occur as the gene is copied or transcribed (called co-transcriptional) and also after the messenger RNA (mRNA) is produced (called post-transcriptional).
The basic type of mRNA targeted for editing is called an imperfect double-stranded RNA—a single-stranded RNA that has folded back onto itself with some mismatched bases. These targeted RNAs can be protein-coding or long non-coding RNAs.

The modification produced by RNA editing is accomplished by protein machinery called adenosine deaminases acting on RNA (ADAR) enzymes. The various types of ADARs, which are creature specific, edit double-stranded RNA, as noted above.

This is most commonly done in non-coding regions of genes (introns) while also editing much fewer sites in coding regions with highly targeted specificity. The RNA editing in introns affects retention of the mRNA in the cell’s nucleus and the process of splicing the RNA to create a mature transcript. Incredibly, the RNA’s encoding ADAR proteins are themselves also commonly edited as part of complex feedback loops and networked interplay between RNA editing and other RNA modification systems.

Interestingly, in some creatures RNA editing is widespread among the RNA encoding of proteins involved in neurotransmission and the cellular electrical machinery that regulates cell signaling, such as
on channels in the cell membrane.
These RNA edits can alter the resulting protein and can also change the splicing pattern of the mRNA when processing the transcript after it’s copied. RNA edits in ion channel proteins dynamically modulate the electrophysiological properties of the neuronal cell’s synapses and other aspects of their neuronal connections to rapidly adapt to various environmental conditions.

Even more amazing from a broader and functional perspective,
RNA editing affects transcripts encoding proteins involved in brain patterning for both embryo development and mature brains, neural cell identity and function, and proteins related to DNA repair. Thus, RNA editing is a key factor in cell neuron activity and brain cell
network plasticity, which is important for daily functioning in things such as memory consolidation.

While the regulatory pathways that control RNA editing are not well understood, research studies show that RNA editing alters the structure and information content of protein-coding and long non-coding RNAs in response to changing environmental conditions and a creature’s past experience.
In this respect, ADAR enzyme activity and target selection have been shown to be linked to cell signaling pathways.

In regard to the adaptive, innate immune response of vertebrates, RNA editing has been shown to be involved as part of the built-in algorithm and learning machinery associated with host responses to viral infections.

Clearly, RNA editing is key to an organism’s ability to develop, grow, and adapt itself in response to its environment and past life experiences.

RNA editing promotes transcriptome diversity
---by recoding and expanding the coding capacity of the genome, typically as a controlled response to changed environmental conditions.

*Evolution pictures living organisms as passive forms being acted on and shaped by outside forces.
*But the more researchers delve into life’s inner workings, the more they find innate, exquisitely engineered systems that enable creatures to adapt and respond to changes around them.
Our world declares the wonders of our Creator, the Lord Jesus Christ."
ICR