Navigation Links
MicroRNAs have shaped the evolution of the majority of mammalian genes

RNA continues to shed its reputation as DNA's faithful sidekick. Now, researchers in the lab of Whitehead Institute Member David Bartel have found that a class of small RNAs called microRNAs influence the evolution of genes far more widely than previous research had indicated.

"MicroRNAs are affecting the majority of protein-coding genes, either at a functional level or an evolutionary level," says Andrew Grimson, a post-doctoral fellow in Bartel's lab.

In order to make a protein, a gene codes for a specific molecule called messenger RNA, or mRNA. Each mRNA molecule contains a blueprint for making a protein. A microRNA can bind to a short sequence on a targeted mRNA and suppress protein production.

In a paper published last January in the journal Cell, Bartel's lab, in collaboration with Chris Burge's lab at MIT, presented evidence that one third of human genes are regulated by microRNAs. In this new study, published online Nov. 24 in Science, the researchers demonstrate that microRNAs affect the expression or evolution of the majority of human genes.

Nearly all genes, the authors explain, contain short sequences that match portions of microRNAs. Some of these potential microRNA target sites are evolutionarily "conserved," meaning that they show up in the same spot on the same gene across species as disparate as the mouse and the chicken. The authors of last January's Cell paper showed that thousands of human genes contain microRNA sites that are conserved in this way. To the extent that evolution has preserved these sites more than would be expected by chance, scientists have regarded them as sites that microRNAs target.

But is a matching sequence all that's required for microRNA targeting and gene regulation, and do nonconserved sites also have the potential to disrupt protein production?

In the new study, scientists in the Bartel lab designed an experiment that zeroed in on these nonconserved targets. Grimson took mRNAs whose target sequences were not conserved and exposed them to microRNAs, which latched on without a problem. The experiment proved that a matching sequence is generally sufficient to disrupt mRNA's ability to make protein.

But while Grimson showed that, at least in the lab, microRNAs could regulate mRNAs with nonconserved sites, the researchers still didn't know the extent to which nonconserved mRNAs coexisted with their matching microRNAs in the natural cell environment. To answer this question, the researchers turned to gene expression patterns of different types of mouse cells.

Kyle Kai-How Farh, a graduate student in Bartel's lab, found that mRNAs with nonconserved sites were generally absent in cells with corresponding microRNAs--more absent than statistical models suggested. The researchers concluded that over the course of evolution many mRNAs, in order to maintain their functions and ensure fitness of the organism, have quickly lost sites that pair up with microRNAs.

In addition to the thousands of cases where genes have avoided microRNA targeting, Farh also investigated the opposite extreme, cases where genes have maintained microRNA target sites over the course of evolution. He found that as immature muscle cells stop dividing and become mature muscle cells, microRNAs are activated and suppress genes that are no longer needed at such high levels in the mature muscle. "Many of these evolutionarily conserved microRNA targets are known to be active in the processes of cell proliferation, development, and cancer," says Farh. "Our genomes have good reason to maintain the microRNA targeting sites necessary for turning down these genes at the appropriate place and time."

An emerging idea is that microRNAs often act to reduce the quantity of protein a gene produces without shutting it off all together. "We think the microRNAs are sometimes having what you can call a dampening effect," says Bartel, who is also a Howard Hug hes Medical Institute investigator and MIT professor of biology. "They appear to be helping cells achieve optimal levels of proteins."

"MicroRNAs are leaving an evolutionary footprint on the majority of the mammalian genome," says Grimson. "Some genes are trying to preserve beneficial microRNA sites and others are evolving in order to avoid developing harmful ones."


'"/>

Source:Whitehead Institute for Biomedical Research


Related biology news :

1. MicroRNAs play a big part in gene regulation - and evolution
2. MicroRNAs can be tumor suppressors
3. MicroRNAs as tumor suppressors
4. Evolution of taste receptor may have shaped human sensitivity to toxic compounds
5. Whats shaped like a pear and has 2 genomes? Check the pond
6. Why is the heart heart-shaped?
7. Molecular biology fills gaps in knowledge of bat evolution
8. Same mutation aided evolution in many fish species, Stanford study finds
9. Researchers trace evolution to relatively simple genetic changes
10. Family trees of ancient bacteria reveal evolutionary moves
11. Great White shark evolution debate involves WSU Lake Campus geology professor
Post Your Comments:
*Name:
*Comment:
*Email:


(Date:6/22/2016)... , June 22, 2016   Acuant ... and verification solutions, has partnered with RightCrowd ... solutions for Visitor Management, Self-Service Kiosks and ... products that add functional enhancements to existing ... corporations and venues with an automated ID ...
(Date:6/16/2016)... 16, 2016 The global ... to reach USD 1.83 billion by 2024, according ... Inc. Technological proliferation and increasing demand in commercial ... to drive the market growth.      ... The development of advanced multimodal techniques for biometric ...
(Date:6/7/2016)...  Syngrafii Inc. and San Antonio Credit Union ... integrating Syngrafii,s patented LongPen™ eSignature "Wet" solution into ... result in greater convenience for SACU members and ... existing document workflow and compliance requirements. ... Highlights: ...
Breaking Biology News(10 mins):
(Date:6/27/2016)... June 27, 2016  Sequenom, Inc. (NASDAQ: ... healthier lives through the development of innovative products and ... the United States denied its petition ... claims of Sequenom,s U.S. Patent No. 6,258,540 (",540 Patent") ... established by the Supreme Court,s Mayo Collaborative Services v. ...
(Date:6/27/2016)...  Liquid Biotech USA , ... Sponsored Research Agreement with The University of Pennsylvania ... cancer patients.  The funding will be used to ... clinical outcomes in cancer patients undergoing a variety ... employed to support the design of a therapeutic, ...
(Date:6/24/2016)... ... 24, 2016 , ... Researchers at the Universita Politecnica delle Marche in Ancona ... or pleural mesothelioma. Their findings are the subject of a new article on the ... are signposts in the blood, lung fluid or tissue of mesothelioma patients that can ...
(Date:6/23/2016)... A person commits a crime, and the detective ... the criminal down. An outbreak of foodborne illness ... (FDA) uses DNA evidence to track down the bacteria that ... It,s not. The FDA has increasingly used a complex, cutting-edge ... illnesses. Put as simply as possible, whole genome sequencing is ...
Breaking Biology Technology: