New research by a team at National Yang-Ming University has indicated a way forward in the treatment of certain hereditary disorders.
Messenger ribonucleic acids (mRNA), which are essential in the production of proteins in eukaryotic genes, including human genes, through translation, are made from nuclear pre-messenger RNAs though a splicing process. Sometimes errors occur in the complex splicing process, leading to the production of mutated proteins.
It had previously been believed that the splicing and translation was a one-way process, but National Science Council-sponsored researcher Cheng Soo-cheng (鄭淑珍), a professor at the university’s Institute of Microbiology and Immunology, said yesterday her research team had found that both of the catalytic steps in splicing were reversible.
Her research was published in the journal Science yesterday.
The research shed new light on how some mutated-protein productions are avoided, as well as how future treatments for certain genetic disorders can be done.
“Nuclear pre-messenger RNAs are the ‘raw materials’ for mRNAs, containing both the non-coding sections called introns, and code-containing sections called exons,” Cheng told a press conference.
In the splicing process, a spliceosome, composed of five small nuclear RNAs and more than 100 protein factors, performs two consecutive transesterification reactions to remove the introns and join the exons, Cheng said, adding that the final product is mature mRNA that is ready to make proteins via a translation process.
“Many hereditary diseases, such as Mediterranean anemia, spinal muscular atrophy and retinitis pigmentosa, are caused by certain gene mutations that affect the splicing process,” she said.
“Traditionally, the protein production paradigm postulates that once a splicing error occurs, the resulting protein is bound to be wrong as well — however, we observed in vitro that under certain conditions, such as fluctuation of pH level, this process can be reversed,” Cheng said.
Cheng’s team, which includes 26-year-old Tseng Chi-kang (曾紀綱), a PhD student working in her lab, speculates that the purpose of the reverse process is to give the cells a “second chance” to produce correctly spliced mRNAs.
“Although we have not confirmed that this process occurs naturally in human cells as well, we hope that, armed with this knowledge, we can develop new treatment methods for diseases that are caused by incorrect splicing,” she said.
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