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: Novel marker discovered for stem cells derived from human umbilical cord blood

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 ...

The controlled cell

Sep 07, 2012

(Phys.org)—An interdisciplinary effort at the Friedrich Miescher Institute for Biomedical Research (FMI) addressed the question of how mRNA content, which is translated into proteins, is regulated in the ...

Recommended for you

New pain relief targets discovered

9 hours ago

Scientists have identified new pain relief targets that could be used to provide relief from chemotherapy-induced pain. BBSRC-funded researchers at King's College London made the discovery when researching ...

Building 'smart' cell-based therapies

10 hours ago

A Northwestern University synthetic biology team has created a new technology for modifying human cells to create programmable therapeutics that could travel the body and selectively target cancer and other ...

Proper stem cell function requires hydrogen sulfide

13 hours ago

Stem cells in bone marrow need to produce hydrogen sulfide in order to properly multiply and form bone tissue, according to a new study from the Center for Craniofacial Molecular Biology at the Herman Ostrow School of Dentistry ...

User comments : 0

More news stories

Chronic inflammation linked to 'high-grade' prostate cancer

Men who show signs of chronic inflammation in non-cancerous prostate tissue may have nearly twice the risk of actually having prostate cancer than those with no inflammation, according to results of a new study led by researchers ...

Turning off depression in the brain

Scientists have traced vulnerability to depression-like behaviors in mice to out-of-balance electrical activity inside neurons of the brain's reward circuit and experimentally reversed it – but there's ...

Better thermal-imaging lens from waste sulfur

Sulfur left over from refining fossil fuels can be transformed into cheap, lightweight, plastic lenses for infrared devices, including night-vision goggles, a University of Arizona-led international team ...

Hackathon team's GoogolPlex gives Siri extra powers

(Phys.org) —Four freshmen at the University of Pennsylvania have taken Apple's personal assistant Siri to behave as a graduate-level executive assistant which, when asked, is capable of adjusting the temperature ...