Navigation Links
Yale scientists identify structure for RNA quality control

A report by Yale scientists in the journal Cell sheds new light on how the protein Ro, a major autoantigen in patients with autoimmune disease, recognizes misfolded RNAs, creating a RNA quality control system for cells.

The quality control process in the cell has been well-studied for the DNA and messenger RNA (mRNA) components for making proteins. However, little was known about what cells do with abnormal or misfolded RNAs that are not translated into protein -- such as ribosomal RNAs (rRNAs), transfer RNAs (tRNAs), and small nuclear and cytoplasmic regulatory RNAs. This work describes a molecular mechanism of RNA quality control.

In the autoimmune disorders systemic lupus erythematosus and Sjogren's syndrome, Ro is known to be an autoantigen, and autoimmune disease develops in mice that lack Ro protein. This study demonstrated a connection between binding of normal RNA and "disposal" of abnormal and misfolded RNAs by Ro protein.

Collaboration between the laboratories of Assistant Professor Karin M. Reinisch and Associate Professor Sandra L. Wolin in the department of Cell Biology used both crystallography and biochemistry to visualize how Ro interacts with these RNAs.

"The crystal structures of Ro revealed two distinct RNA binding sites, one of which recognizes misfolded small RNAs. Unlike most proteins, Ro has a hole through the middle - and the hole is used in distinguishing these RNAs," said Reinisch.

Mothers with anti-Ro antibodies often have babies with heart signal conduction defects; some scientists believe that the antibodies may cause the defects. "Although Ro is a major human autoantigen, how the molecule is recognized by patient autoantibodies was not fully determined. So, understanding these features of the Ro protein may allow the design of drugs to block the interaction between the antibodies and Ro," said Wolin.

The research team consisted of members from the Reinisch and Wolin lab groups-- Adam J. Ste in, Gabriele Fuchs, Chumei Fu. Wolin is also an investigator of the Howard Hughes Medical Institute. The work was funded by grants from the G. Harold and Leila Y. Mathers Foundation, the Pew Charitable Trust, and the National Institutes of Health. A report by Yale scientists in the journal Cell sheds new light on how the protein Ro, a major autoantigen in patients with autoimmune disease, recognizes misfolded RNAs, creating a RNA quality control system for cells.

The quality control process in the cell has been well-studied for the DNA and messenger RNA (mRNA) components for making proteins. However, little was known about what cells do with abnormal or misfolded RNAs that are not translated into protein -- such as ribosomal RNAs (rRNAs), transfer RNAs (tRNAs), and small nuclear and cytoplasmic regulatory RNAs. This work describes a molecular mechanism of RNA quality control.

In the autoimmune disorders systemic lupus erythematosus and Sjogren's syndrome, Ro is known to be an autoantigen, and autoimmune disease develops in mice that lack Ro protein. This study demonstrated a connection between binding of normal RNA and "disposal" of abnormal and misfolded RNAs by Ro protein.

Collaboration between the laboratories of Assistant Professor Karin M. Reinisch and Associate Professor Sandra L. Wolin in the department of Cell Biology used both crystallography and biochemistry to visualize how Ro interacts with these RNAs.

"The crystal structures of Ro revealed two distinct RNA binding sites, one of which recognizes misfolded small RNAs. Unlike most proteins, Ro has a hole through the middle - and the hole is used in distinguishing these RNAs," said Reinisch.

Mothers with anti-Ro antibodies often have babies with heart signal conduction defects; some scientists believe that the antibodies may cause the defects. "Although Ro is a major human autoantigen, how the molecule is recognized by patient autoantibodies was not fully determined. So, understanding these features of the Ro protein may allow the design of drugs to block the interaction between the antibodies and Ro," said Wolin.

The research team consisted of members from the Reinisch and Wolin lab groups-- Adam J. Stein, Gabriele Fuchs, Chumei Fu. Wolin is also an investigator of the Howard Hughes Medical Institute. The work was funded by grants from the G. Harold and Leila Y. Mathers Foundation, the Pew Charitable Trust, and the National Institutes of Health.


'"/>

Source:Yale University


Related biology news :

1. Wisconsin scientists grow critical nerve cells
2. UCSB scientists probe sea floor venting to gain understanding of early life on Earth
3. UAB scientists discover the origin of a mysterious physical force
4. Fox Chase Cancer Center scientists identify immune-system mutation
5. Weizmann Institute scientists develop a new approach for directing treatment to metastasized prostate cancer in the bones.
6. U-M scientists find genes that control growth of common skin cancer
7. UCLA scientists transform HIV into cancer-seeking missile
8. RNA project to create language for scientists worldwide
9. Carnegie Mellon scientists develop tool that uses MRI to visualize gene expression in living animals
10. To control germs, scientists deploy tiny agents provocateurs
11. Leprosy microbes lead scientists to immune discovery
Post Your Comments:
*Name:
*Comment:
*Email:


(Date:12/6/2016)... -- Valencell , the leading innovator in performance ... third consecutive year of triple digit growth for its ... a 360 percent increase in companies who have acquired ... by sales of its wrist and ear Benchmark™ sensor ... for hearables for fitness and healthcare applications. ...
(Date:12/2/2016)... AUSTIN, Texas , Dec. 1, 2016 /PRNewswire/ ... provider, today announced BioLock , an electrocardiogram ... and health monitoring, a key IoT asset. The ... embedded into a vehicle,s steering wheel and mobile ... a simple touch. As vehicle technology ...
(Date:11/29/2016)... 29, 2016   Neurotechnology , a ... recognition technologies, today released FingerCell 3.0, a ... solutions that run on low-power, low-memory microcontrollers. ... less than 128KB of memory, enabling it ... have limited on-board resources, such as: mobile ...
Breaking Biology News(10 mins):
(Date:12/8/2016)... ... 08, 2016 , ... This CAST literature review and report looks at problems ... on the economic effects in countries that are major global commodity exporters and importers, ... resultant risk of low level presence (LLP) puts large volumes of trade worth billions ...
(Date:12/8/2016)...  HedgePath Pharmaceuticals, Inc. (OTCQX: HPPI), a clinical ... to commercialize innovative therapeutics for patients with cancer, ... approved for trading on the OTCQX U.S. market. ... effective today, under the ticker symbol "HPPI." ... must meet high financial standards, follow best practice ...
(Date:12/8/2016)... Dec. 8, 2016  Partnering to fuel ... Technology Partners of Southeastern Pennsylvania ... parent company of Independence Blue Cross; and Safeguard Scientifics ... intentions for a $6 million funding initiative over a ... Responding to a burgeoning economic vitality in ...
(Date:12/7/2016)... ... 2016 , ... A new study published in the just-published ... advanced pancreatic cancer, liquid biopsies are not yet an adequate substitute for tissue ... sampling may improve the value of a blood-based test.” The study was conducted ...
Breaking Biology Technology: