14 RNA Processing

StudyBlue printing of 14 RNA Processing html, body, div, span, applet, object, iframe, h1, h2, h3, h4, h5, h6, p, blockquote, pre, a, abbr, acronym, address, big, cite, code, del, dfn, em, font, img, ins, kbd, q, s, samp, small, strike, strong, sub, sup, tt, var, b, u, i, center, fieldset, form, label, legend, table, caption, tbody, tfoot, thead, tr, th, td { margin: 0; padding: 0; border: 0; outline: 0; font-size: 100%; background: transparent; } body { line-height: 1; } blockquote, q { quotes: none; } blockquote:before, blockquote:after, q:before, q:after { content: ''; content: none; } /* remember to define focus styles! */ :focus { outline: 0; } /* remember to highlight inserts somehow! */ ins { text-decoration: none; } del { text-decoration: line-through; } /* tables still need 'cellspacing="0"' in the markup */ table { border-collapse: collapse; border-spacing: 0; } /* end RESET */ .header { min-width:800px; } .logo { padding:6px 20px 2px 20px; margin:0; font-size:25px; font-weight:bold; color:#808285; position:relative; border-bottom: 1px solid #c5c5c5; } .logo-blue { color:#70adc4; } .logo-desc { font-weight:normal; font-size:19px; color:#cccccc; margin-top:50px; position:absolute; display: none; } .back-button { position:absolute; top:20px; right:20px; font-size:13px; line-height:25px; color:rgb(0,175,225); font-weight:normal; } .back-button a { color:rgb(0,175,225); } .instructions { padding:0; margin:0; width:100%; position:relative; color:rgb(100,100,100); } .step-holder { border-left:1px solid #ededed; margin-left:20px; } .steps { padding:15px 0; float:left; width:24%; border-right:1px solid #ededed; text-align:center; } .steps-01 { } .steps-02 { } .steps-03 { } .steps-04 { } .label { padding:5px 10px; } .print-button { } .print-button a { background-color:rgb(0,175,225); color:white; line-height: 19px; padding:9px 8px 5px 30px; font-size:14px; text-decoration:none; background-image: url(images/printer.png); background-repeat: no-repeat; background-position: 7px 50%; -moz-border-radius: 5px; -webkit-border-radius: 5px; } .print-button a:hover { background-color:black; } .theNote .content { width: 8.0in !important; margin: 5px auto; padding:20px; background-color:white; } .theNote .header { border-bottom: 1px dashed #C8C8C8; font-size: 17px; padding: 0 0 10px; line-height: 19px; color: #00ADE1; min-width:500px; } .theNote .body { font-size: 14px; line-height: 19px; padding: 10px 0; } .theNote{ padding:6px 0; clear:both; background-color: rgb(200,200,200); } .theNote h3{ color: rgb(100,100,100); } .theNote h1, .theNote h3{ background-color:white; padding:2px 20px; width:8.0in !important; margin: 0 auto; font-size: 15px; } .theNote h1{ padding-top: 10px; font-size: 15px; } .theNote h1:first-child{ font-size: 20px; } .theNote h3 { font-size: 14px; font-weight: normal; } #options { border: 3px double #ccc; padding: 5px 12px; margin: 10px 50px 10px 20px; float: left; } #info { border-top: 1px solid #ccc; padding-top: 5px; font-style: italic; } li { margin: 5px 10px 5px 25px; } ul li { list-style: disc; } ol li { list-style: decimal; } img { border: 0; } table { clear: both; width: 100%; border: 1px solid #c5c5c5; border-width: 1px 0; margin: 0; page-break-after: always; } table#page { page-break-after: auto; } td { text-align: center; font-size: 12px; border-bottom: 1px dashed #c5c5c5; height: 1.75in; width: 50%; padding-left: 15px; } .leftside { border-right: 1px solid #cccccc; padding: 0 15px 0 0; } .bottom td { border-bottom: none; } .clearfix { clear:both; line-height:1px; height:1px; } img { max-width:80%; max-height:150px; margin:20px; } @media print {.header { display: none; } .content .header{ display:inherit; } table { border: 1px dashed #bbb; border-width: 1px 0; } .theNote{ background-color:white; } } 1. tRNA and rRNA processing tRNA and rRNA are often synthesized as longer precursors, requiring processing to become final products Processed by intron splicing, cleavage, and trimming. Some precursors can be cut to product several rRNAs as well as tRNAs. 2. RNA enzymes-ribozymes Catalytic RNAs RNase P catalyzes transesterification to remove the 5' part of the pre-tRNA, composed of M1 RNA and 14kD protein subunit Even though RNA alone is catalytically active, the protein component of RNase P changes the properties of the enzyme HDV is linear RNA that undergoes self cleavage, making it a HDV ribozyme 3. RNA editing Changes individual nucleotides in pre-RNA to produce mature RNA. C to U deaminase U deletion/insertion by different enzymes Alipoprotein B gene can become shorter or longer due to the C to U change. Intestines, C to U produces a stop codon and results into a smaller protein ApoB-48 In the liver, this RNA editing does not happen, and results in full protein ApoB-100, related to high stroke and heart attack rates 4. RNA degradation Decapping pathway - 5' to 3' exonucleases Deadenylation - 3' to 5' exonucleases Endonuclease - endonucleases that cuts out internal sequences regardless of tail or CAP. Regulation of mRNA translation is controlled by the speed of degradation of mRNA Iron control of mRNA degradation Transferrin moves iron into the cell Ferritin removes iron from the cell When iron is HIGH, IRE-BP does not bind to IRE, allowing TfR mRNA is degraded, so less iron is put into the cell When iron is LOW, IRE-BP binds to IRE, preventing TfR mRNA from being degraded, putting more iron into the cell (TfR = transferritin) Iron control of mRNA translation When iron concentrations are HIGH, IRE-BP does not bind to IRE. Ferritin mRNA free of IRE-BP is translated to produce ferritin, removing excess When iron concentrations are LOW. IRE-BP binds to IRE to prevent ferritin mRNA from being translated 5. miRNA, siRNA, and RNAi miRNA - Micro RNA, binds to target mRNA by imperfect base pairing to suppress translation or trigger degradation Some genes encode miRNA RNAi - and siRNA - RNA interference and short interferring RNA. Uses dsRNA to suppress gene expression. By perfect pairing, triggers degradation of target mRNAs Usually happens by introduction of dsRNA Used routinely to knock-down gene expression in both animals and plants. Discovered from anti-sense RNA knock down technology Overexpressed mRNA can form stem loops of dsRNA, resulting in siRNA and RNAi because many copies of mRNA will hybridize together and create dsRNA. This creates siRNA and RNAi. Overexpression = too much RNA essentially siRNA - cells synthesize to suppress RNA virus replication and suppresion of expression of some transposons often amplified, which may be associated to its ability to suppress viral infection. RdRP (RNA-dependent RNA polymerase) uses siRNA as a primer and the target mRNA as templates to synthesize more dsRNA, which are substrates for additional siRNA production miRNA - synthesized as a common regulating molecule to control gene expression. somewhat analogous to cells that produce protein degradation machinery to control protein level Dual function of miRNA In plants, it functions as a degradation signal In animals, suppresses translation miRNA and siRNA are produced from long dsRNA precursors by a ribonuclease/RNA helicase called DICER Virus introduces dsRNA Dicer recognizes dsRNA and breaks it down into smaller forms of dsRNA RISC (RNA induced silencing complex) converts dsRNA into ssRNA ssRNA forms perfect or imperfect base pairing with target mRNA to suppress its translation or trigger its degradation. RISC is also involved (This is a way to protect the cell from virus attacks) RNAi used to "knockdown" gene expression Targeted suppression by RNAi (called knockdown) tested for cancer. however two challenges in RNAi therapy Because it's small, siRNA often acts on off-targets, side effects siRNA is degraded rapidly because its small RNAi technology can be used for viral diseases in plants. This is due to simple transgenic technology and easiness of finding specific sequences of viral genome This allows for virus-resistant crops in agriculture 6. RNA and evolution Miller-Urey experiment attempted to recreate the atmosphere in the beginning times of life and see if organic life could be created from inorganic materials Created amino acids, bases, sugars, and fatty acids. Biomolecule creation possible from inorganic materials Condensation - allows for spontaneous polymerization Polymers to protocells lipid molecules are known to aggregate together and form liposomes. Liposomes are also known to engulf other polymers to form protocells RNA as genetic material new strands of RNA can be formed by binding to individual nucleotides of the old strand. RNA can be copied and stored RNA is used as genetic material today (for viruses only) RNA as catalysts Reactions catalyzed by naturally occuring ribozymes Transesterification Phosphoryl transfer Peptidyl transfer Why is RNA neither the genetic material nor the major catalytic molecule? Proteins are more complex, allows for more versatility DNA is more stable than RNA, so DNA is better for storing RNA simply acts as a middle man Protein enzymes later evolved to direct DNA synthesis. DNA genomes eventually replaced RNA as major genetic material.