Navigation Links
RNA splicing occurs in nerve-cell dendrites

Researchers at the University of Pennsylvania School of Medicine have discovered that nerve-cell dendrites have the capacity to splice messenger RNA (pre-mRNA), a process once believed to only take place in the nucleus of cells.

By uncovering this capability in dendrites, the investigators hope to relate this capacity to memory and learning, as well as cognitive dysfunction. Senior author James Eberwine, PhD, Professor of Pharmacology, and lead authors Kevin Miyashiro, and Jason Glanzer, PhD, both in Eberwine's lab, report their findings in this week's early online edition of the Proceedings of the National Academy of Sciences.

Dendrites, which branch from the cell body of the neuron, play a key role in the communication between cells of the nervous system, allowing for many neurons to connect with each other to form a network. Dendrites detect the electrical and chemical signals transmitted to the neuron by the axons of other neurons. The synapse is the neuronal structure where this chemical connection is formed, and investigators surmise that the synapse is where learning and memory occur.

Researchers have long agreed that mRNA splicing takes place within the cell nucleus. In the nucleus of a mammalian cell, a gene is copied into mRNA, which possesses both exons (mature mRNA regions destined to code for proteins) and introns (non-coding regions). mRNA splicing works by cutting out introns and merging together the remaining exon pieces, resulting in an mRNA capable of being translated into a specific protein.

The vast array of proteins within the human body arises in part from the many ways that mRNAs can be spliced and reconnected. Specifically, splicing removes pieces of intron and exon regions from the RNA, with the resulting spliced RNA often being made into protein. Should the RNA have different exons spliced in and out of it, then different proteins can be made from this RNA. The Eberwine lab was successful in showing that s plicing can occur in dendrites because they have employed very sensitive technologies developed in their lab, which permits the detection and quantification of RNA splicing as well as the translated protein in single isolated dendrites.

"In addition to showing that mRNA splicing occurs in dendrites in which we added mRNA, we also detected the resulting protein," notes Eberwine. "Since the splicing machinery is present in dendrites, one could speculate that if pre-mRNA is present naturally in the dendrite, when activated, it may be spliced and translated, giving rise to many different proteins."

Protein diversity is a key aspect to the complexity of the central nervous system. Proteins are the workhorses of the cell and are generally responsible for insuring that cells function properly. When proteins interact with one another they can elicit specific physiological responses, including the generation and maintenance of memories. Changing protein identity, as can occur with splicing, can change the ability of the protein to interact with other proteins and therefore potentially change such physiological processes. With the dendrite being the initial site in the neuron where learning is thought to occur, the ability to create a diversity of mRNAs, through local splicing, and subsequent protein translation may permit exquisitely sensitive control of these cellular functions.

"The regulation and timing of the expression of proteins is what makes the central nervous system function," says Eberwine. The diversity and redundancy of the nervous-system proteins may serve to help maintain the system over a lifetime. However, failure in protein regulation or proper expression in neurons may give rise to cognitive dysfunction. "Most neurodegenerative and psychiatric illnesses exhibit dendrite dysfunction, therefore, the inability to properly generate spliced RNAs in dendrites or proteins may underlie aspects of these disease processes."

By revealing the capacity of mRNA splicing in dendrites, the investigators hope to develop an understanding of its role in cognition and dysfunction. Eberwine and colleagues are now working to find an endogenous mRNA that will undergo splicing within dendrites.

Co-authors in addition to Eberwine, Glanzer, and Miyashiro are Jai-Yoon Sul, Lindy Barrett, Brian Belt, and Phillip Haydon, all from Penn. This worked was funded by the National Institute on Aging and the National Institute on Mental Health.


'"/>

Source:University of Pennsylvania School of Medicine


Related biology news :

1. Protein splicing upsets the DNA colinearity paradigm
2. RNA map provides first comprehensive understanding of alternative splicing
3. RNA splicing factor implicated in ovarian tumor cell growth
4. OHSU study says stem cell fusion occurs in tumors
5. 3 proteins may play important role in nerve-cell repair
Post Your Comments:
*Name:
*Comment:
*Email:


(Date:3/6/2017)... March 6, 2017 Mintigo , ... today announced Predictive Sales Coach TM , its ... sales intelligence into Salesforce. This unique AI application ... sales organizations with deep knowledge of their customers ... intelligent engagement. Predictive Sales Coach extends Mintigo,s existing ...
(Date:3/2/2017)... -- Summary This report provides all the ... its partnering interests and activities since 2010. Download ... Partnering Deals and Alliance since 2010 report provides an ... the world,s leading life sciences companies. On ... inclusion of the most up to date deal and ...
(Date:3/2/2017)... Australia , March 2, 2017 Australian ... Ltd (ASX: CYP), has signed an agreement with ... from the Monash Biomedicine Discovery Institute and Department of ... to conduct a further preclinical study to support the ... treatment of asthma.  Asthma is a ...
Breaking Biology News(10 mins):
(Date:3/27/2017)... (PRWEB) , ... March 27, 2017 , ... ... method to engineer scalable and customizable vascular grafts in JoVE’s Video Journal, the ... lead to new and improved ways of treating coronary artery disease (CAD). Lam ...
(Date:3/24/2017)... , March 24, 2017  Infectex Ltd., a ... today announced positive results of a Phase 2b-3 clinical ... regimen in patients with multidrug-resistant pulmonary tuberculosis (MDR-TB). SQ109 ... at Sequella, Inc. ( USA ) and ... A total of 140 patients were enrolled in a ...
(Date:3/24/2017)... Agenus Inc. (NASDAQ: AGEN), an immuno-oncology company ... vaccines, today announced participation at the following conferences: ... and Maidstone Life Sciences conference "Cancer Immunotherapy Conference" at ... New York, NY . Agenus will participate in ... am: Robert B. Stein , M.D., Ph.D., President, ...
(Date:3/23/2017)... 23, 2017  SeraCare Life Sciences, Inc., a ... vitro diagnostics manufacturers and clinical laboratories, is ... multiplexed Inherited Cancer reference material ... next-generation sequencing (NGS). The Seraseq™ Inherited Cancer DNA ... from industry experts to validate the ability ...
Breaking Biology Technology: