In this Fallen World, apparently a "kill Switch" flipped off in our ancestors immune system at some point (likely when the population was small).
Q: Now, can the minds that God gave humans figure out how to turn it back on?
"Alternative RNA splicing functions like a film editor rearranging scenes from the same footage to create different versions of a movie. By selecting which segments to retain or discard, the editor can shape the final product into a drama, comedy, or thriller, all using the same raw material.
Similarly, cells modify RNA splicing to generate different proteins from a single gene, allowing them to adapt and regulate function as needed. However, when cancer disrupts this process, it can drive tumor growth and survival by altering normal splicing patterns.
A recent study published in Nature Communications by researchers from The Jackson Laboratory (JAX) and UConn Health reveals how
cancer hijacks this precise RNA splicing mechanism.
"Alternative RNA splicing functions like a film editor rearranging scenes from the same footage to create different versions of a movie. By selecting which segments to retain or discard, the editor can shape the final product into a drama, comedy, or thriller, all using the same raw material.
Similarly, cells modify RNA splicing to generate different proteins from a single gene, allowing them to adapt and regulate function as needed. However, when cancer disrupts this process, it can drive tumor growth and survival by altering normal splicing patterns.
A recent study published in Nature Communications by researchers from The Jackson Laboratory (JAX) and UConn Health reveals how
More importantly, the study introduces a potential therapeutic approach that could slow or even shrink aggressive, treatment-resistant tumors. This breakthrough has the potential to revolutionize treatment strategies for challenging cancers, such as triple-negative breast cancer and certain brain tumors, where effective therapies remain scarce.
Olga Anczuków, an associate professor at JAX and co-program leader at the NCI-designated JAX Cancer Center, are tiny genetic elements called poison exons, nature’s own “off switch” for protein production.
Olga Anczuków, an associate professor at JAX and co-program leader at the NCI-designated JAX Cancer Center, are tiny genetic elements called poison exons, nature’s own “off switch” for protein production.
When these exons are included in an RNA message, they trigger its destruction before a protein can be made—preventing harmful cellular activity. In healthy cells, poison exons regulate the levels of key proteins, keeping the genetic machinery in check. But in cancer, this safety mechanism often fails.
Furthermore, the team found a correlation between levels of poison exons and patient outcomes. “We’ve shown for the first time that low levels of poison exon inclusion in the TRA2β gene are associated with poor outcomes in many different cancer types, and especially in aggressive and difficult-to-treat cancers,” said Anczuków. These include breast cancer, brain tumors, ovarian cancers, skin cancers, leukemias, and colorectal cancers, Anczuków explained.
Anczuków, Leclair, and Brugiolo then went on to see if they could increase the inclusion of the poison exon in the TRA2β gene and reactivate the kill switch.
Furthermore, the team found a correlation between levels of poison exons and patient outcomes. “We’ve shown for the first time that low levels of poison exon inclusion in the TRA2β gene are associated with poor outcomes in many different cancer types, and especially in aggressive and difficult-to-treat cancers,” said Anczuków. These include breast cancer, brain tumors, ovarian cancers, skin cancers, leukemias, and colorectal cancers, Anczuków explained.
Anczuków, Leclair, and Brugiolo then went on to see if they could increase the inclusion of the poison exon in the TRA2β gene and reactivate the kill switch.
---They found their answer in antisense oligonucleotides (ASOs)—synthetic RNA fragments that can be designed to increase poison exon inclusion in specific ways. When introduced into cancer cells, ASOs effectively flipped the genetic switch, restoring the body’s natural ability to degrade excess TRA2β RNA and inhibit tumor progression.
“We found that ASOs can rapidly boost poison exon inclusion, essentially tricking the cancer cell into turning off its own growth signals,” said Leclair. “These poison exons work like a rheostat, quickly adjusting protein levels—and that could make ASOs a highly precise and effective therapy for aggressive cancers.”
“We found that ASOs can rapidly boost poison exon inclusion, essentially tricking the cancer cell into turning off its own growth signals,” said Leclair. “These poison exons work like a rheostat, quickly adjusting protein levels—and that could make ASOs a highly precise and effective therapy for aggressive cancers.”
SciTechDaily
