Thread by @janiesaysyay

Hey Mr. DeeJay I just wanna hear some rhythm and blues music

on the 📻

Don't wanna discuss it

Think it's time for a change

You may get disgusted
Start thinkin' that I'm strange...

That case I'll go underground
Get some heavy rest

Never have to worry
About what is worst or what is best

Oh oh

Scientists created a new tool "circle sequencing" to explore transcription (copying DNA into mRNA) errors and found that transcript errors create proteins with amyloid and prion properties. >

Domino

"Here, we demonstrate that transcript errors generate amyloid and prion-like proteins in a wide variety of human cell types, including stem cells, brain organoids, and fully differentiated neuron" >

Misfolded, or mistake proteins, self-assemble into longer amyloid fibers, these protein aggregates are associated with a large number of diseases associated with aging: cancer, diabetes, heart disease and with neurodegeneration: Alzheimer's, Parkinsons, CJD. >

Mistakes in RNA synthesis (from the original DNA) or RNA editing can cause these mutant, amyloid proteins to be made. >

These mutant proteins can bind to nearby healthy proteins and cause them to misfold too, one after another, like dominos falling in a line on top of each other. >

This contributes to disease in the body, depriving cells of healthy proteins and dysregulating cell function . >

Using circle sequencing, 🧑‍🔬s proved that RNA
transcription errors do indeed cause amyloid and
prion-like proteins to be made, and that these mutant
proteins successfully convert nearby healthy or
"Wild Type" proteins into mutants.

They showed DNA damage caused the process. >

Transcription showed a similar error rate and spectrum.
The transcriptions errors they found correlate with known amyloid/prion-like proteins which cause certain diseases. >

When the mutant proteins were made, they were recognized by the cell as mutants and excluded from the nucleus (whereas healthy WT proteins were not) and then formed into large protein deposits in the cytoplasm. This is a hallmark of disease. >

Romeo my Romeo

When the mutant proteins and healthy WT proteins were coexpressed in the same cells, the WT proteins were also excluded from the nucleus. They were converted into mutants and formed aggregates with the other mutants. 💞 >

There you go >

Lord have mercy

They used bioinformatics to find more errors and uncover new mutant proteins. >

I said oh oh

They looked at p53, the tumor suppressor protein. >

Domino

"Adding the TP53S149F amyloid seed solution to WT TP53 in a 1:100 ratio induced fibril growth.

O. Protein aggregates created by mutant TP53 form spontaneously and can be seen by the naked eye (arrow.)" >

Say it again

I said oh oh
Domino

I said oh oh
Domino
>

"a limited number of mutant transcripts is sufficient to initiate this process...for prions, there may be no safe dose at all." >

>

Dig it! >

Hey!

Transcriptional mutagenesis is abundant and long
lasting. >

DNA damage > RNA damage for generating transcript errors. >

Hey!

RNA-editing technologies (ZFN, TALENS, Cas9) can have off-target editing events which also cause the formation of large numbers of mutant proteins. This is a key finding which has huge implications for the gene editing industry. >

I said oh oh oh

Non-genetic causes of mutant protein formation, DNA damage, RNA damage, can generate the same mutant proteins responsible for neurodegenerative and age related diseases like Alzheimer's and cancer.

Why is this paper important? >

Domino

Gene therapy, (the COVID 💉) has the potential to cause DNA damage and RNA damage in the transcription phase of creating mRNA during the process of producing large amounts of DNA and mRNA in bacterial batches for commercial use. >

This research shows that a small % of DNA and RNA transcript errors can generate a sustained, and in some cases, a large amount of mutant proteins.

The mRNA created from such progenitors could express this mutant protein potential, generating amyloids and prion-like proteins. >

Hey Mister Deejay

I just wanna hear
some
rhythm and blues 🎶

on the 📻
on the 📻
on the 📻

#Domino #Transcription #Mutagenesis #Amyloidosis #Prions #neurdegeneration #Alzheimers #Parkinsons #cancer #TurboCJD #TurboCancers #GeneTherapy #pandemicplaylist

Neuroscientist Dr. Kevin McCairn reads the paper and explains the implications of the research:

https://x.com/NestCommander/status/1742576910398525896?s=20

The SARS2 viral proteins can cause amyloidosis >

https://x.com/pizzapicklespur/status/1742937676402372792?s=20

A theory that a tiny amount of frameshifting during protein translation can cause the pathological misfolded proteins found in BSE and CJD.
If true, the dangers of mRNA transfection rise exponentially.

"One per million frameshifted prions."

https://x.com/CumberpatchM/status/1743573978709438642?s=20