Need microRNA processing? Get Smad

Jun 11, 2008

Researchers at Tufts University School of Medicine and Tufts Medical Center have found that Smad proteins regulate microRNA (miRNA) processing. Understanding the role of Smad proteins enables researchers to investigate abnormal miRNA processing which is a contributing factor in development of cardiovascular disorders and cancer. The study was published online today in Nature.

"We found that Smad proteins, the signal carriers of a group of proteins that help regulate cells, promote the processing of a subset of microRNA, including miR-21. Smad proteins control the processing of miRNA from a primary copy of RNA (pri-miRNA) to precursor miRNA (pre-miRNA)," explains corresponding and senior author Akiko Hata, PhD, assistant professor at Tufts University School of Medicine and a member of the biochemistry program faculty at the Sackler School of Graduate Biomedical Sciences.

"Smad proteins move to the nucleus of the cell and interact with a specific complex, called the Drosha microprocessor complex, to promote the processing of pri-miR-21 to pre-miR-21, eventually leading to an increase in mature miR-21 levels."

"Mature miR-21 targets a tumor suppressor gene important for programmed cell death in both cancer cells and in smooth muscle cells, the cells that help our veins and arteries contract and relax," contextualizes Brandi Davis, first author, and PhD candidate in the department of biochemistry at Tufts University School of Medicine. "Abnormal miRNA processing is a contributing factor in cardiovascular disorders and cancer, yet little is known about its regulation."

Hata, Davis and colleagues designed a series of experiments to determine how members of a super-family of growth factors, called the transforming growth factor β (TGFβ) family, which is a group of proteins that help regulate cellular functions, can cause miRNA levels to increase. By exposing cells to members of the TGFβ family, the researchers were able to observe that, over time, levels of pre-miR-21 and mature miR-21 increased, while levels of pri-miR-21 did not change.

"Since pri-miR-21 levels did not change, we concluded that the TGFβ family of growth factors doesn't begin to play a role in miRNA processing until the pri-miRNA to pre-miRNA step," explains Hata, who is also an investigator in the Molecular Cardiology Research Institute (MCRI) at Tufts Medical Center.

"Smad proteins were thought to act exclusively by regulating the transcription of DNA into messenger RNA (mRNA) in response to TGFβ signaling. This finding reveals a new role of Smad proteins as regulators of miRNA processing," comments Giorgio Lagna, PhD, co-author, investigator in the MCRI at Tufts Medical Center and also an assistant professor at Tufts University School of Medicine. "If we want to generate a drug that regulates signaling by TGFβ, we now have the option to target different pathways downstream of TGFβ and achieve much more specific outcomes."

MiRNAs are small gene products that regulate gene expression by interaction with mRNA. The role of mRNA in a cell is to carry the instructions for making proteins from the DNA in the nucleus to another part of the cell where the instructions are carried out and the proteins are made.

"Thus, cells with abnormal miRNA levels may have abnormal protein levels, putting the organism at risk for many diseases including cancer and cardiovascular disorders. More research needs to be done to elucidate further the roles of miR-21 and other miRNA molecules," explains Hata "because better understanding of how miRNAs effect disease may lead to a clearer understanding of disease initiation and progression."

Source: Tufts University, Health Sciences

Explore further: 2,500-year-old Pythagoras theorem helps to show when a patient has turned a corner

add to favorites email to friend print save as pdf

Related Stories

Human Argonaute proteins: To slice or not to slice?

Jun 06, 2013

What makes one Argonaute a slicer and another one not? Human Argonaute proteins are key players in the gene regulation process known as RNA interference, RNAi. Professor Joshua-Tor's group of Cold Spring Harbor Laboratory ...

Recommended for you

Stem cells faulty in Duchenne muscular dystrophy

16 hours ago

Like human patients, mice with a form of Duchenne muscular dystrophy undergo progressive muscle degeneration and accumulate connective tissue as they age. Now, researchers at the Stanford University School of Medicine have ...

Here's how the prion protein protects us

21 hours ago

The cellular prion protein (PrPC) has the ability to protect the brain's neurons. Although scientists have known about this protective physiological function for some time, they were lacking detailed knowledge ...

Regulation of maternal miRNAs in early embryos revealed

22 hours ago

The Center for RNA Research at the Institute for Basic Science (IBS) has succeeded in revealing, for the first time, the mechanism of how miRNAs, which control gene expression, are regulated in the early embryonic stage.

User comments : 0

Please sign in to add a comment. Registration is free, and takes less than a minute. Read more

Click here to reset your password.
Sign in to get notified via email when new comments are made.