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Credit: UC San Diego
School of Medicine
Scientists say they have identified a protein that broadly regulates how genetic information transcribed from DNA to messenger RNA (mRNA) is processed and ultimately translated into the myriad proteins necessary for life.
The group’s work shows that the protein ADR-1 binds to mRNA and then enhances RNA editing.
This process allows a gene to be present as multiple mRNAs that can each affect gene expression differently.
The research appears in Cell Reports.
“Problems with RNA editing show up in many human diseases, including those of neurodegeneration, cancer, and blood disorders,” said study author Gene Yeo, PhD, of the University of California, San Diego.
“This is the first time that a single protein has been identified that broadly regulates RNA editing. There are probably hundreds more. Our approach provides
a method to screen for them and opens up new ways to study human biology and disease.”
Using the model organism Caenorhabditis elegans, Dr Yeo and his colleagues identified more than 400 new mRNA editing sites. As the majority of them were regulated by ADR-1, the team declared the protein the first global regulator of RNA editing.
“What we’ve determined is that this protein’s ability to alter editing of mRNAs is not specific to just a few genes, but, instead, its ability to bind to mRNAs is required for proper RNA editing of most mRNAs,” said study author Michael C. Washburn, of Indiana University in Bloomington.
The group found that the region of ADR-1 protein that binds to target mRNAs in C elegans is required for regulating editing. This region is present in many human proteins, and a protein similar to ADR-1 is specifically expressed in human neurons.
“So it is likely that a similar mechanism exists to regulate editing in humans,” said study author Heather A. Hundley, PhD, also of Indiana University.
“Further work in our lab will be aimed at understanding the detailed mechanism of how these proteins regulate editing, in turn providing an inroad to developing therapeutics that modulate editing for the treatment of human diseases.”
C elegans, like humans, highly expresses a family of proteins in the nervous system called adenosine deaminases acting on RNA (ADARs), a family that includes ADR-1.
ADARs change specific nucleotides in RNA in a process called adenosine-to-inosine editing (A-to-I editing) that diversifies genetic information to specify different amino acids, splice sites, and structures.
Scientists currently estimate there are between 400,000 and 1 million A-to-I editing events in noncoding regions of the human transcriptome.
Newly synthesized RNA encodes the exact information found in DNA. But it’s when later RNA editing occurs that RNA gets altered, and this change is most often catalyzed by ADARs.
“One thing we also know is that ADAR protein levels are not altered in disease, implying that other mechanisms are also at work regulating ADAR-mediated RNA editing,” Dr Hundley said. “By identifying this major regulator of noncoding editing in C elegans, we can now focus on dissecting the regulatory mechanism and determining the conservation of this regulatory protein in human cells.” 
Credit: UC San Diego
School of Medicine
Scientists say they have identified a protein that broadly regulates how genetic information transcribed from DNA to messenger RNA (mRNA) is processed and ultimately translated into the myriad proteins necessary for life.
The group’s work shows that the protein ADR-1 binds to mRNA and then enhances RNA editing.
This process allows a gene to be present as multiple mRNAs that can each affect gene expression differently.
The research appears in Cell Reports.
“Problems with RNA editing show up in many human diseases, including those of neurodegeneration, cancer, and blood disorders,” said study author Gene Yeo, PhD, of the University of California, San Diego.
“This is the first time that a single protein has been identified that broadly regulates RNA editing. There are probably hundreds more. Our approach provides
a method to screen for them and opens up new ways to study human biology and disease.”
Using the model organism Caenorhabditis elegans, Dr Yeo and his colleagues identified more than 400 new mRNA editing sites. As the majority of them were regulated by ADR-1, the team declared the protein the first global regulator of RNA editing.
“What we’ve determined is that this protein’s ability to alter editing of mRNAs is not specific to just a few genes, but, instead, its ability to bind to mRNAs is required for proper RNA editing of most mRNAs,” said study author Michael C. Washburn, of Indiana University in Bloomington.
The group found that the region of ADR-1 protein that binds to target mRNAs in C elegans is required for regulating editing. This region is present in many human proteins, and a protein similar to ADR-1 is specifically expressed in human neurons.
“So it is likely that a similar mechanism exists to regulate editing in humans,” said study author Heather A. Hundley, PhD, also of Indiana University.
“Further work in our lab will be aimed at understanding the detailed mechanism of how these proteins regulate editing, in turn providing an inroad to developing therapeutics that modulate editing for the treatment of human diseases.”
C elegans, like humans, highly expresses a family of proteins in the nervous system called adenosine deaminases acting on RNA (ADARs), a family that includes ADR-1.
ADARs change specific nucleotides in RNA in a process called adenosine-to-inosine editing (A-to-I editing) that diversifies genetic information to specify different amino acids, splice sites, and structures.
Scientists currently estimate there are between 400,000 and 1 million A-to-I editing events in noncoding regions of the human transcriptome.
Newly synthesized RNA encodes the exact information found in DNA. But it’s when later RNA editing occurs that RNA gets altered, and this change is most often catalyzed by ADARs.
“One thing we also know is that ADAR protein levels are not altered in disease, implying that other mechanisms are also at work regulating ADAR-mediated RNA editing,” Dr Hundley said. “By identifying this major regulator of noncoding editing in C elegans, we can now focus on dissecting the regulatory mechanism and determining the conservation of this regulatory protein in human cells.”
Credit: UC San Diego
School of Medicine
Scientists say they have identified a protein that broadly regulates how genetic information transcribed from DNA to messenger RNA (mRNA) is processed and ultimately translated into the myriad proteins necessary for life.
The group’s work shows that the protein ADR-1 binds to mRNA and then enhances RNA editing.
This process allows a gene to be present as multiple mRNAs that can each affect gene expression differently.
The research appears in Cell Reports.
“Problems with RNA editing show up in many human diseases, including those of neurodegeneration, cancer, and blood disorders,” said study author Gene Yeo, PhD, of the University of California, San Diego.
“This is the first time that a single protein has been identified that broadly regulates RNA editing. There are probably hundreds more. Our approach provides
a method to screen for them and opens up new ways to study human biology and disease.”
Using the model organism Caenorhabditis elegans, Dr Yeo and his colleagues identified more than 400 new mRNA editing sites. As the majority of them were regulated by ADR-1, the team declared the protein the first global regulator of RNA editing.
“What we’ve determined is that this protein’s ability to alter editing of mRNAs is not specific to just a few genes, but, instead, its ability to bind to mRNAs is required for proper RNA editing of most mRNAs,” said study author Michael C. Washburn, of Indiana University in Bloomington.
The group found that the region of ADR-1 protein that binds to target mRNAs in C elegans is required for regulating editing. This region is present in many human proteins, and a protein similar to ADR-1 is specifically expressed in human neurons.
“So it is likely that a similar mechanism exists to regulate editing in humans,” said study author Heather A. Hundley, PhD, also of Indiana University.
“Further work in our lab will be aimed at understanding the detailed mechanism of how these proteins regulate editing, in turn providing an inroad to developing therapeutics that modulate editing for the treatment of human diseases.”
C elegans, like humans, highly expresses a family of proteins in the nervous system called adenosine deaminases acting on RNA (ADARs), a family that includes ADR-1.
ADARs change specific nucleotides in RNA in a process called adenosine-to-inosine editing (A-to-I editing) that diversifies genetic information to specify different amino acids, splice sites, and structures.
Scientists currently estimate there are between 400,000 and 1 million A-to-I editing events in noncoding regions of the human transcriptome.
Newly synthesized RNA encodes the exact information found in DNA. But it’s when later RNA editing occurs that RNA gets altered, and this change is most often catalyzed by ADARs.
“One thing we also know is that ADAR protein levels are not altered in disease, implying that other mechanisms are also at work regulating ADAR-mediated RNA editing,” Dr Hundley said. “By identifying this major regulator of noncoding editing in C elegans, we can now focus on dissecting the regulatory mechanism and determining the conservation of this regulatory protein in human cells.”