Navigation Links
Penn study identifies molecular guardian of cell's RNA

PHILADELPHIA - When most genes are transcribed, the nascent RNAs they produce are not quite ready to be translated into proteins - they have to be processed first. One of those processes is called splicing, a mechanism by which non-coding gene sequences are removed and the remaining protein-coding sequences are joined together to form a final, mature messenger RNA (mRNA), which contains the recipe for making a protein.

For years, researchers have understood the roles played by the molecular machines that carry out the splicing process. But, as it turns out, one of those familiar components plays a new, and altogether unexpected role.

As senior author Gideon Dreyfuss, PhD, the Isaac Norris Professor of Biochemistry and Biophysics at the University of Pennsylvania School of Medicine and colleagues report in Nature, one of the splicing machinery's components called U1 has a second, equally important role in gene expression: To enable gene sequences to be read out into their RNA transcripts in their entirety, rather than have that process prematurely stopped. Dreyfuss is also a Howard Hughes Medical Institute Investigator.

The researchers revealed an unexpected function for U1 in protecting mRNA transcripts from premature termination in addition to and independent of its role in splicing.

As Dreyfuss puts it, "U1 is a guardian of the transcriptome." The transcriptome is the set of all RNA molecules in one cell.

U1 is one of a collection of RNA-protein complexes, called snRNPs, that recognize splicing junctions, excise non-coding gene sequences called introns, and join the remaining coding sequences called exons together. The Dreyfuss team previously showed that loss of SMN, a protein that helps assemble snRNPs and is deficient in individuals with the common neurodegenerative disease spinal muscular atrophy (SMA), results in altered snRNP levels and abnormal splicing.

SMN deficiency affects all snRNPs to one degree or another. The Dreyfuss team wanted to find out what would happen if just one snRNP was missing. They started with U1.

The team's expectation was that they would detect an increase in unspliced RNA transcripts, and indeed they saw evidence of that. But, to their surprise, the majority of the genes produced a very different and striking result. Their transcripts terminated prematurely and abruptly, generally within a relatively short distance from the transcription start site of the gene.

When they sequenced the ends of the resulting truncated RNAs, they found that they had been prematurely cleaved and tagged with a long string of nucleotide building blocks called adenine. This string is a hallmark of a process called cleavage-and-polyadenylation, which normally occurs at the end of a gene's RNA transcript. The lack of U1 was causing the cleavage/polyadenylation machinery to kick into gear early.

The implication, Dreyfuss says, is that U1's normal role, in addition to splicing, is to keep the cleavage/polyadenylation machinery in check until the RNA polymerase enzyme that synthesizes the transcript reaches its finish line. The researchers propose a model in which U1 binds throughout the nascent RNA transcripts, stymieing the cleavage/polyadenylation machinery that tags along with the moving polymerase complex. This in turn protects the many potential polyadenylation signals encountered along the way, and could explain the relative abundance of U1 in cells compared to other snRNPs. The additional U1 corresponds to the greater amount needed for its additional function.

"The transcripts are under constant threat from the cleavage/polyadenylation machinery," Dreyfuss explains. "This machinery doesn't patiently wait for the transcript to reach the end of the gene; rather, the nascent RNA transcripts are subject to becoming attacked by this machinery. It's a constant danger they face, and the U1 snRNP suppresses it."

It is, he says, "a novel role" for U1, and a critical component for correctly making mRNA. "It is essential for the integrity of the transcriptome, the landscape of all mRNA molecules in the cell," he concludes.


Contact: Karen Kreeger
University of Pennsylvania School of Medicine

Related biology news :

1. LSUHSC study IDs proteins regulating water retention in salt-sensitive hypertension
2. Offshore wind a mixed bag: University of Maryland study
3. Modeling study identifies characteristics of high elk-use areas in western Oregon, Washington
4. Universities receive grants to study climate change decisions
5. Center to study effects of plastics chemicals on childrens health
6. Study of tiny magnets may advance their use in microelectronics
7. BMC receives National Institutes of Health grant to study intrauterine cocaine and substance reslience
8. CRN responds to JAMA fish oil study
9. Singapore scientists first to perform genome-wide study of human stem cells
10. Shifting forms: Penn study shows how variations of same protein affect immune response
11. First babies born from genetic screening study
Post Your Comments:
Related Image:
Penn study identifies molecular guardian of cell's RNA
(Date:10/27/2015)... YORK , Oct. 27, 2015 In ... major issues of concern for various industry verticals such ... is due to the growing demand for secure & ... in various ,sectors, such as hacking of bank accounts, ... for electronic equipment such as PC,s, laptops, and smartphones ...
(Date:10/26/2015)... October 26, 2015 ... adds Biometrics Market Shares, ... as well as Emerging Biometrics Technologies: ... to its collection of IT and ... . --> ...
(Date:10/23/2015)... 23, 2015 Research and Markets ( ... Voice Recognition Biometrics Market 2015-2019" report to their ... The global voice recognition biometrics market to grow ... --> --> The report, ... based on an in-depth market analysis with inputs from ...
Breaking Biology News(10 mins):
(Date:12/1/2015)... 2015  CardioCell LLC, a Stemedica Cell Technologies ... cardiovascular indications, intends to proceed with finalizing a ... from a Heart Failure Advisory Board comprising cardiology ... Board members . In a recent meeting members ... and efficacy data from CardioCell,s on-going chronic heart ...
(Date:12/1/2015)...  Symic, a clinical-stage biotherapeutics company developing multiple compounds ... announced that it has secured $25 million in a ... its lead candidates SB-030 and SB-061. The financing was ... all existing major investors, as well as several new ... by Symic to over $43 million since being founded ...
(Date:12/1/2015)... Texas (PRWEB) , ... December 01, 2015 , ... Matthew ... his new post, VerMilyea will oversee all IVF lab procedures as well ... and fertility preservation. , “We traveled 7,305 miles to Auckland, New Zealand to bring ...
(Date:11/30/2015)... ... 30, 2015 , ... Global Stem Cells Group ... the Santiago Marriott. The Global Stem Cells Group GMP facility is equipped with ... qualified medical researchers and practitioners, experienced in administering stem cell protocols using highly ...
Breaking Biology Technology: