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Lindsey-Jordan

Page history last edited by LJordan 14 years, 11 months ago

Ribozyme: The RNA Enzyme 

 

 

Table of Contents

I. Mechanism

 

II. Ribozyme

     A. Discovery

     B. Types

          1. Hairpin

          2. Hammerhead

          3. RNase P

          4. Group I Introns

     C. Function

 

III. Structure

 

IV. Therapeutic Agents

 

                          

                                              Hairpin Ribozyme 

 

 

 

 

 


 

 

I. MECHANISM

          Ribozymes, or ribonucleic acid enzymes, are RNA structures that catalyze specific chemical reactions.  This RNA enzyme is mainly used in translation during the synthesis of proteins from mRNA.  Ribozymes have the ability to cut target RNA molecules or seal up RNA molecules by ligation (Lilley and Eckstein 2008).  RNA is also modified by a self-cleaving mechanism of the ribozyme, breaking the phosphodiester bonds (www.ncbi.gov).  Figure 1 shows the ribozyme cleaving the mRNA strand, which inactivates it and is no longer able to function.  A more detailed mechanism of self-cleaving ribozymes can be found at www.nature.com.

 

                                                                  Ribozyme Mechanism in Translation:

                                                             YouTube plugin error

 

 


 

 II. RIBOZYME

 

A. Discovery:

          Thomas R. Cech and Sidney Altman discovered the catalyst function of ribozymes in the 1980's while studying RNA splicing in Tetrahymena thermophila at Yale University (http://www.hhmi.org).  They won the Nobel Prize in 1989 in chemistry for showing that RNA can act as a biological enzyme in addition to a genetic messenger (http://www.hhmi.org).  Before this discovery, it was believed that proteins were the only enzymes that catalyzed reactions (www.users.rcn.com).  Additional information on Thomas Cech and his research on the ribozyme can be found at www.nobelprize.org.  

 

Video:  Thomas Cech discussing the double life of RNA and it's catalytic properties.

 

 

B. Types:

          1. Hairpin

                 This ribozyme is found in the RNA of plant viruses and functions in controlling gene expression along with RNA replication (www.ncbi.nlm.nih.gov).  The mechanism of the hairpin involves cleavage and ligation reactions that are described in a study by Walter and Burke.  A detailed overview of the ribozyme and its role in replication are described in Figure 2

 

          2. Hammerhead 

                 Self-cleavage reactions allow this ribozyme to result in two RNA products (www.callutheran.edu). It is found in viroids and also in the RNA of plant viruses.  Information on the structure and function of the hammerhead ribozyme is explained in a study conducted by Verma, Vaish, and Eckstein.  The cleavage reactions and formation of the stem loop structure can be seen in Figure 3. 

                                                                         

          3. RNase P

                 The function of this ribozyme is also cleaving RNA, mainly to eliminate extra sequences of transfer RNA (www.wikipedia.org).  One interesting fact about RNase P is it's ability to recognize the structures of tRNA instead of the RNA sequences (Kim et al. 2004).  RNase P has also been proven to block gene expression in some human viruses (Kim et al. 2004). Figure 4 shows the secondary and tertiary structure of the RNase P enzyme.  More information regarding the regulation of RNase P can be found at www.pubmedcentral.nih.gov.

 

                                         Figure 4

                                       

          

 

            4. Group I Introns

                   These ribozymes are capable of splicing their own RNA transcript.  Figure 5 shows the splicing of the introns by catalysis reactions.  The database for Group I introns can be found at www.rna.whu.edu.  A study by Dotson, Johnson, and Testa shows additional information of Group I introns acting as a catalyst for splicing reactions.  

 

Video:  Key features of ribozyme splicing by Group I introns.

 

 

C. Function:

       The general function of all ribozymes is to catalyze biological reactions by cleaving site-specific sequences on RNA at a free 2' OH end, resulting in mature strands of RNA (www.academic.brooklyn.cuny.edu). After binding to target RNA by Watson-Crick base pairing, ribozymes cut the RNA and cause it to inactivate.  After cleaving the strand, the ribozyme freely disassociates (www.academic.brooklyn.cuny.edu).  For general information of ribozymes, The Ribozyme Web Page has a collection of links and research articles relating to different types of ribozymes.  Figure 6 shows the three major steps involved in ribozyme catalysis during translation.

 

                              Figure 6

                     

 

 

 


 

 

III. STRUCTURE

 

         Using X-ray crystallography, a crystal structure can be viewed to determine a ribozyme's unique properties, arrangement, and specificity (www.wikipedia.org).  The discovery of the hammerhead ribozyme crystal structure allowed scientists to learn about the tertiary interactions that stabilizes the structure and the accuracy of RNA folding (Lilley and Eckstein 2008).  It also helps explain how RNA is packaged and its role as an enzyme to catalyze reactions (Lilley and Eckstein 2008).  Figure 7 shows the crystal structure of the hammerhead ribozyme.

                            

                                          Figure 7

                                  

 

The links below have additional information of specific ribozyme crystal structures:

 


 

IV. THERAPEUTIC AGENTS

 

        Some ribozymes can be important for controlling gene expression in certain diseases or viruses like HIV, asthma, or Hepatitis C (www.pubmedcentral.nih.gov).  Studies have been conducted to determine if ribozymes can cleave target RNA to inactivate protein synthesis (www.online.karger.com).  Figure 8 shows the HIV cycle and possible binding sites for ribozymes to inactivate the infection.  The Journal of Medicinal Chemistry discusses various roles in which ribozymes could act as therapeutic agents. 

 

                                                                                    Figure 8

                                                                          


 

External Links: 

 

Comments (1)

Christopher Korey said

at 8:43 am on Apr 7, 2009

Looks good. As you convert the outline to text, Remember to be concise about each subsection and provide link outs to other pages or papers that provide more in depth detail if that is required. If someone wants more information give them a way to find it not necessarily put it on the page. I like the ribozyme video you found. Try to divide the sections by inserting a horizontal bar. Remember to reference just like any other paper, images as well.

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