Using proteomics, transcriptomics and genomic data form over 10,000 human samples were analyzed deeply, samples also included 6 cancer types and 26 healthy human tissues. The analysis discovered that Alternate RNA translation were more abundant than their canonical counterparts of hundreds of proteins, which suggests that there is sense-codon recoding.
What are these alternate translations?
We all know about the OG Central dogma where DNA transcribes into RNA and RNA translates into Proteins(constituting the 20 canonical amino acids).
Studies suggests that this last step of RNA translation into proteins might not be that straight forward where we see 20 canonical amino acids forming all the functional proteins of our body.
It can rather sometimes go as,
DNA to RNA to RNA processing and modifications which leads to formation of multiple possible protein products, which turns to different proteofroms with different unknown cellular functions.
For the reference please see the infographics attached below
Sense Codon recoding: It is the basis for genetic code expansion. It involves incorporation of non-canonical amino acids(ncAAs) into proteins. In the absence of genetic mutations and RNA editing non canonical amino acids may arise from alternate translation. Often considered as translational errors but various studies suggest they also confer beneficial functions.
How can same RNA produce different proteins?
That is where sense codon recoding comes in. In sense codon recoding a codon that normally transcribes to one particular protein can read the code differently and introduce another amino acid which is non-canonical. They can be called as recoded proteins.
Recoded proteins includes transcription factors, proteases, signaling proteins and proteins associated with neurodegeneration.
Its significance
The study demonstrated that there is positive correlation between alternate translation and diversification of mammalian proteome. It further suggests:
- Alternate translation produces thousands of stable and abundant proteins in human and mouse tissue.
- Some of alternate translations are more frequent in tumors suggesting a disease association.
- Substitutions are also seen abundantly in neurodegenerative diseases.
Sources:https://www.biorxiv.org/content/10.1101/2024.08.26.609665v4.full#sec-12
How is expansion of genetic code going to be beneficial to us share your thoughts?
MBH/AB