0
0

Chapter 2. Basic Principles of Molecular Biology and Genomics

Jiang-Zhou Yu, M.D., Ph.D.; Mark M. Rasenick, Ph.D.
DOI: 10.1176/appi.books.9781585623860.416279

Sections

Excerpt

In June 2000, it was announced that both a corporate effort and a government consortium had succeeded in sequencing all of the human genome. This was followed by the publication of that sequence in February 2001 (Lander et al. 2001; Venter et al. 2001). For anyone involved in biology or medicine, these events represented a revolution in the technical and conceptual approach to both research and therapy.

Your session has timed out. Please sign back in to continue.
Sign In Your Session has timed out. Please sign back in to continue.
Sign In to Access Full Content
 
Username
Password
Sign in via Athens (What is this?)
Athens is a service for single sign-on which enables access to all of an institution's subscriptions on- or off-site.
Not a subscriber?

Subscribe Now/Learn More

PsychiatryOnline subscription options offer access to the DSM-5 library, books, journals, CME, and patient resources. This all-in-one virtual library provides psychiatrists and mental health professionals with key resources for diagnosis, treatment, research, and professional development.

Need more help? PsychiatryOnline Customer Service may be reached by emailing PsychiatryOnline@psych.org or by calling 800-368-5777 (in the U.S.) or 703-907-7322 (outside the U.S.).

FIGURE 2–1. Diagram of a typical neuron.As described in the text, this neuron is divided into zones for the reception of signals (input = dendrites), integration of signals (regulation = nucleus and soma), conduction of signals (axon), and transmission of signals (axon terminal).

FIGURE 2–2. Transcription factors and RNA polymerase II complex.Typical transcription factors contain DNA-binding domains, protein dimerization domains, and transcription activation domains. Some transcription factors (e.g., cAMP response element–binding protein [CREB]) may be modified by phosphorylation. The transcription activation domain interacts with an RNA polymerase II (Pol II) complex to induce transcription. TATA binding protein (TBP) binds to the TATA box element and associates with general transcription factors (TFII). This gene transcription apparatus recruits Pol II to the appropriate gene.

FIGURE 2–3. Activation of cAMP response element–binding protein (CREB) via different signal transduction pathways.Signal cascades are activated by external stimuli, such as hormones or neurotransmitters and growth factors. Arrows indicate the interaction between pathways. AC = adenylyl cyclase; C = catalytic subunits of PKA; Ca++ = calcium; CaMK IV = calmodulin-dependent kinase IV; cAMP = cyclic 3'-5'-adenosine monophosphate; CBP = CREB-binding protein; Epac = exchange protein activated by cAMP; ERK = extracellular-regulated kinase; Gs = subunit of the stimulatory G protein; P = phosphorylation; PKA = cAMP–dependent protein kinase; R = regulatory subunits of PKA; Rap and Ras = small GTPases (small proteins that bind to guanosine triphosphate [GTP]); RSK2 = ribosomal S6 kinase 2.

FIGURE 2–4. Transcription and RNA splicing.The horizontal black line between exons indicates an intron. The region before the first exon is the 5' regulatory region of the gene, such as a TATA box. There also are cis-regulatory elements in introns and downstream of the last exon. The heterogeneous nuclear RNA (hnRNA), containing both exons and introns, is spliced to form mRNA. mRNAs are then exported from the nucleus to the cytoplasm, where they will direct the synthesis of distinct proteins.

FIGURE 2–5. Outline of gene cloning.See text for details.

FIGURE 2–6. Schematic of the mechanism of RNA interference (RNAi) posttranscriptional knockdown of a gene product.The procedure starts with introduction (transfection, electroporation, or injection) of double-stranded RNA (dsRNA) or small interfering RNA (siRNA) into cells, or expression of small hairpin RNA (shRNA) in cells with vectors encoding shRNAs. The cellular ribonuclease (RNase) Dicer recognizes the long dsRNA molecules and shRNA. Subsequently the dsRNA is cleaved, resulting in 21-nt RNA duplexes, the siRNAs. These siRNA molecules are then incorporated into the RNA-induced silencing complex (RISC) multiprotein complex, where they are unwound by an adenosine triphosphate (ATP)–dependent process, transforming the complex into an active state. Activated RISC uses one strand of the RNA as a bait to bind homologous RNA molecules. The target RNA is cleaved and degraded, resulting in gene silencing.

FIGURE 2–7. Conventional gene disruption ("knockout").(A) Producing chimeric mice. First, a mutant allele is produced by replacing the coding exons of the desired gene with a neomycin (neo) cassette and transferring it into embryonic stem (ES) cells. Second, genetically altered ES cells are reintroduced into a developing blastocyst, where they contribute to the developing embryo. (B) Breeding chimeric mice. When the germ cells of the resulting chimeric mouse (chimera) are ES cell–derived (germ-line mutation), the heterozygotes (+/–) can be produced by breeding. One-half of the offspring will be heterozygous. The heterozygous animals may be bred to produce homozygous mice (–/–). TK = thymidine kinase; WT = wild type.

References

Abe K, Sato S, Kawagoe J, et al: Isolation and expression of an ischaemia-induced gene from gerbil cerebral cortex by subtractive hybridization. Neurol Res 15:23–28, 1993
[PubMed]
 
Allen JA, Yu JZ, Donati RJ, et al: Beta-adrenergic receptor stimulation promotes G alpha s internalization through lipid rafts: a study in living cells. Mol Pharmacol 67:1493–1504, 2005
[PubMed]
 
Allen JA, Halverson-Tamboli RA, Rasenick MM: Lipid raft microdomains and neurotransmitter signalling. Nat Rev Neurosci 8:128–140, 2007
[PubMed]
 
Ali NJ, Levine MS: Changes in expression of N-methyl-D-aspartate receptor subunits occur early in the R6/2 mouse model of Huntington's disease. Dev Neurosci 28:230–238, 2006
[PubMed]
 
Amarzguioui M, Rossi JJ, Kim D: Approaches for chemically synthesized siRNA and vector-mediated RNAi. FEBS Lett 579:5974–5981, 2005
[PubMed]
 
Ballestar E, Esteller M: The impact of chromatin in human cancer: linking DNA methylation to gene silencing. Carcinogenesis 23:1103–1109, 2002
[PubMed]
 
Barkats M, Bemelmans AP, Geoffroy MC, et al: An adenovirus encoding CuZnSOD protects cultured striatal neurones against glutamate toxicity. Neuroreport 7:497–501, 1996
[PubMed]
 
Bass BL: RNA editing and hypermutation by adenosine deamination. Trends Biochem Sci 22:157–162, 1997
[PubMed]
 
Bass BL: RNA editing by adenosine deaminases that act on RNA. Annu Rev Biochem 71:817–846, 2002
[PubMed]
 
Bemelmans AP, Horellou P, Pradier L, et al: Brain-derived neurotrophic factor-mediated protection of striatal neurons in an excitotoxic rat model of Huntington's disease, as demonstrated by adenoviral gene transfer. Hum Gene Ther 10:2987–2997, 1999
[PubMed]
 
Benraiss A, Chmielnicki E, Lerner K, et al: Adenoviral brain-derived neurotrophic factor induces both neostriatal and olfactory neuronal recruitment from endogenous progenitor cells in the adult forebrain. J Neurosci 21:6718–6731, 2001
[PubMed]
 
Berg KA, Cropper JD, Niswender CM, et al: RNA-editing of the 5 HT(2C) receptor alters agonist-receptor-effector coupling specificity. Br J Pharmacol 134:386–392, 2001
[PubMed]
 
Berry M, Barrett L, Seymour L, et al: Gene therapy for central nervous system repair. Curr Opin Mol Ther 3:338–349, 2001
[PubMed]
 
Bornemann KD, Staufenbiel M: Transgenic mouse models of Alzheimer's disease. Ann N Y Acad Sci 908:260–266, 2000
[PubMed]
 
Brummelkamp TR, Bernards R, Agami R: A system for stable expression of short interfering RNAs in mammalian cells. Science 296:550–553, 2002
[PubMed]
 
Bulyk ML, Gentalen E, Lockhart DJ, et al: Quantifying DNA-protein interactions by double-stranded DNA arrays. Nat Biotechnol 17:573–577, 1999
[PubMed]
 
Burns CM, Chu H, Rueter SM, et al: Regulation of serotonin-2C receptor G-protein coupling by RNA editing. Nature 387:303–308, 1997
[PubMed]
 
Carter RJ, Lione LA, Humby T, et al: Characterization of progressive motor deficits in mice transgenic for the human Huntington's disease mutation. J Neurosci 19:3248–3257, 1999
[PubMed]
 
Cepeda C, Starling AJ, Wu N, et al: Increased GABAergic function in mouse models of Huntington's disease: reversal by BDNF. J Neurosci Res 78:855–867, 2004
[PubMed]
 
Cha JH, Kosinski CM, Kerner JA, et al: Altered brain neurotransmitter receptors in transgenic mice expressing a portion of an abnormal human huntington disease gene. Proc Natl Acad Sci U S A 95:6480–6485, 1998
[PubMed]
 
Chalfie M, Tu Y, Euskirchen G, et al: Green fluorescent protein as a marker for gene expression. Science 263:802–805, 1994
[PubMed]
 
Chang HS, Lin CH, Chen YC, et al: Using siRNA technique to generate transgenic animals with spatiotemporal and conditional gene knockdown. Am J Pathol 165:1535–1541, 2004
[PubMed]
 
Chen H, Lambert NA: Endogenous regulators of G protein signaling proteins regulate presynaptic inhibition at rat hippocampal synapses. Proc Natl Acad Sci U S A 97:12810–12815, 2000
[PubMed]
 
Collins FS: Positional cloning moves from perditional to traditional. Nat Genet 9:347–350, 1995
[PubMed]
 
Coumoul X, Shukla V, Li C, et al: Conditional knockdown of Fgfr2 in mice using Cre-LoxP induced RNA interference. Nucleic Acids Res 33:e102, 2005
 
DeCerbo J, Carmichael GG: SINEs point to abundant editing in the human genome. Genome Biol 6:216, 2005
[PubMed]
 
Doyu M, Sawada K, Mitsuma N, et al: Gene expression profile in Alzheimer's brain screened by molecular indexing. Brain Res Mol Brain Res 87:1–11, 2001
[PubMed]
 
Dragatsis I, Levine MS, Zeitlin S: Inactivation of Hdh in the brain and testis results in progressive neurodegeneration and sterility in mice. Nature genetics 26:300–306, 2000
[PubMed]
 
Dunah AW, Jeong H, Griffin A, et al: Sp1 and TAFII130 transcriptional activity disrupted in early Huntington's disease. Science 296:2238–2243, 2002
[PubMed]
 
Duyao MP, Auerbach AB, Ryan A, et al: Inactivation of the mouse Huntington's disease gene homolog Hdh. Science 269:407–410, 1995
[PubMed]
 
Eberwine J, Yeh H, Miyashiro K, et al: Analysis of gene expression in single live neurons. Proc Natl Acad Sci U S A 89:3010–3014, 1992
[PubMed]
 
Eriksson M, Taskinen M, Leppa S: Mitogen activated protein kinase-dependent activation of c-Jun and c-Fos is required for neuronal differentiation but not for growth and stress response in PC12 cells. J Cell Physiol 210:538–548, 2007
[PubMed]
 
Fire A, Xu S, Montgomery MK, et al: Potent and specific genetic interference by double-stranded RNA in Caenorhabditis elegans. Nature 391:806–811, 1998
[PubMed]
 
Geng C, Pellegrino A, Bowman J, et al: Complete RNAi rescue of neuronal degeneration in a constitutively active Drosophila TRP channel mutant. Biochim Biophys Acta 1674:91–97, 2004
[PubMed]
 
Gil JM, Rego AC: Mechanisms of neurodegeneration in Huntington's disease. Eur J Neurosci 27:2803–2820, 2008
[PubMed]
 
Gilchrist A, Bunemann M, Li A, et al: A dominant-negative strategy for studying roles of G proteins in vivo. J Biol Chem 274:6610–6616, 1999
[PubMed]
 
Ginsberg SD, Hemby SE, Lee VM, et al: Expression profile of transcripts in Alzheimer's disease tangle-bearing CA1 neurons. Ann Neurol 48:77–87, 2000
[PubMed]
 
Graves L, Dalvi A, Lucki I, et al: Behavioral analysis of CREB alpha-delta mutation on a B6/129 F1 hybrid background. Hippocampus 12:18–26, 2002
[PubMed]
 
Grosjean H, Auxilien S, Constantinesco F, et al: Enzymatic conversion of adenosine to inosine and to N1-methylinosine in transfer RNAs: a review. Biochimie 78:488–501, 1996
[PubMed]
 
Gusella JF, Wexler NS, Conneally PM, et al: A polymorphic DNA marker genetically linked to Huntington's disease. Nature 306:234–238, 1983
[PubMed]
 
Halliday KR, Stein PJ, Chernoff N, et al: Limited trypsin proteolysis of photoreceptor GTP-binding protein: light- and GTP-induced conformational changes. J Biol Chem 259:516–525, 1984
[PubMed]
 
Harding TC, Geddes BJ, Noel JD, et al: Tetracycline-regulated transgene expression in hippocampal neurones following transfection with adenoviral vectors. J Neurochem 69:2620–2623, 1997
[PubMed]
 
He TC, Zhou S, da Costa LT, et al: A simplified system for generating recombinant adenoviruses. Proc Natl Acad Sci U S A 95:2509–2514, 1998
[PubMed]
 
Hengst U, Cox LJ, Macosko EZ, et al: Functional and selective RNA interference in developing axons and growth cones. J Neurosci 26:5727–5732, 2006
[PubMed]
 
Ho LW, Brown R, Maxwell M, et al: Wild type huntingtin reduces the cellular toxicity of mutant huntingtin in mammalian cell models of Huntington's disease. J Med Genet 38:450–452, 2001
[PubMed]
 
Hodgson JG, Agopyan N, Gutekunst CA, et al: A YAC mouse model for Huntington's disease with full-length mutant huntingtin, cytoplasmic toxicity, and selective striatal neurodegeneration. Neuron 23:181–192, 1999
[PubMed]
 
Hong J, Yoshida K, Rosner MR: Characterization of a cysteine proteinase inhibitor induced during neuronal cell differentiation. J Neurochem 81:922–934, 2002
[PubMed]
 
Hsiao K, Chapman P, Nilsen S, et al: Correlative memory deficits, Abeta elevation, and amyloid plaques in transgenic mice. Science 274:99–102, 1996
[PubMed]
 
Hughes SM, Moussavi-Harami F, Sauter SL, et al: Viral-mediated gene transfer to mouse primary neural progenitor cells. Mol Ther 5:16–24, 2002
[PubMed]
 
Imaizumi K, Tsuda M, Imai Y, et al: Molecular cloning of a novel polypeptide, DP5, induced during programmed neuronal death. J Biol Chem 272:18842–18848, 1997
[PubMed]
 
Janus C, Phinney AL, Chishti MA, et al: New developments in animal models of Alzheimer's disease. Curr Neurol Neurosci Rep 1:451–457, 2001
[PubMed]
 
Jouvenceau A, Potier B, Battini R, et al: Glutamatergic synaptic responses and long-term potentiation are impaired in the CA1 hippocampal area of calbindin D(28k)-deficient mice. Synapse 33:172–180, 1999
[PubMed]
 
Kable ML, Heidmann S, Stuart KD: RNA editing: getting U into RNA. Trends Biochem Sci 22:162–166, 1997
[PubMed]
 
Kan L, Hu M, Gomes WA, Kessler JA: Transgenic mice overexpressing BMP4 develop a fibrodysplasia ossificans progressiva (FOP)-like phenotype. Am J Pathol 165:1107–1115, 2004
[PubMed]
 
Katsuki M, Sato M, Kimura M, et al: Conversion of normal behavior to shiverer by myelin basic protein antisense cDNA in transgenic mice. Science 241:593–595, 1988
[PubMed]
 
Kaziro Y, Itoh H, Kozasa T, et al: Structure and function of signal-transducing GTP-binding proteins. Annu Rev Biochem 60:349–400, 1991
[PubMed]
 
Keshet I, Lieman-Hurwitz J, Cedar H: DNA methylation affects the formation of active chromatin. Cell 44:535–543, 1986
[PubMed]
 
Kim DH, Rossi JJ: Strategies for silencing human disease using RNA interference. Nat Rev Genet 8:173–184, 2007
[PubMed]
 
Kim DH, Behlke MA, Rose SD, et al: Synthetic dsRNA Dicer substrates enhance RNAi potency and efficacy. Nat Biotechnol 23:222–226, 2005
[PubMed]
 
Kohara K, Kitamura A, Morishima M, et al: Activity-dependent transfer of brain-derived neurotrophic factor to postsynaptic neurons. Science 291:2419–2423, 2001
[PubMed]
 
Kornberg RD, Lorch Y: Twenty-five years of the nucleosome, fundamental particle of the eukaryote chromosome. Cell 98:285–294, 1999
[PubMed]
 
Koshimizu H, Araki T, Takai S, et al: Expression of CD47/integrin-associated protein induces death of cultured cerebral cortical neurons. J Neurochem 82:249–257, 2002
[PubMed]
 
Kubista M: Nucleic acid-based technologies: application amplified. Pharmacogenomics 5:767–773, 2004
[PubMed]
 
Kubista M, Andrade JM, Bengtsson M, et al: The real-time polymerase chain reaction. Mol Aspects Med 27:95–125, 2006
[PubMed]
 
Lander ES, Linton LM, Birren B, et al: Initial sequencing and analysis of the human genome. Nature 409:860–921, 2001
[PubMed]
 
Lauver A, Yuan LL, Jeromin A, et al: Manipulating Kv4.2 identifies a specific component of hippocampal pyramidal neuron A-current that depends upon Kv4.2 expression. J Neurochem 99:1207–1223, 2006
[PubMed]
 
Leavitt BR, Guttman JA, Hodgson JG, et al: Wild-type huntingtin reduces the cellular toxicity of mutant huntingtin in vivo. Am J Hum Genet 68:313–324, 2001
[PubMed]
 
Leavitt BR, van Raamsdonk JM, Shehadeh J, et al: Wild-type huntingtin protects neurons from excitotoxicity. J Neurochem 96:1121–1129, 2006
[PubMed]
 
Liang P, Averboukh L, Keyomarsi K, et al: Differential display and cloning of messenger RNAs from human breast cancer versus mammary epithelial cells. Cancer Res 52:6966–6968, 1992
[PubMed]
 
Lind K, Stahlberg A, Zoric N, et al: Combining sequence-specific probes and DNA binding dyes in real-time PCR for specific nucleic acid quantification and melting curve analysis. Biotechniques 40:315–319, 2006
[PubMed]
 
Lione LA, Carter RJ, Hunt MJ, et al: Selective discrimination learning impairments in mice expressing the human Huntington's disease mutation. J Neurosci 19:10428–10437, 1999
[PubMed]
 
Liu J, Lamb D, Chou MM, et al: Nerve growth factor-mediated neurite outgrowth via regulation of Rab5. Mol Biol Cell 18:1375–1384, 2007
[PubMed]
 
Liu QR, Zhang PW, Zhen Q, et al: KEPI, a PKC-dependent protein phosphatase 1 inhibitor regulated by morphine. J Biol Chem 277:13312–13320, 2002
[PubMed]
 
Lucki I, Dalvi A, Mayorga AJ: Sensitivity to the effects of pharmacologically selective antidepressants in different strains of mice. Psychopharmacology (Berl) 155:315–322, 2001
[PubMed]
 
Maas S, Melcher T, Seeburg PH: Mammalian RNA-dependent deaminases and edited mRNAs. Curr Opin Cell Biol 9:343–349, 1997
[PubMed]
 
Mangiarini L, Sathasivam K, Seller M, et al: Exon 1 of the HD gene with an expanded CAG repeat is sufficient to cause a progressive neurological phenotype in transgenic mice. Cell 87:493–506, 1996
[PubMed]
 
Marcotte EM: How do shotgun proteomics algorithms identify proteins? Nat Biotechnol 25:755–757, 2007
[PubMed]
 
Markert CL: Fertilization of mammalian eggs by sperm injection. J Exp Zool 228:195–201, 1983
[PubMed]
 
Mello CV, Jarvis ED, Denisenko N, et al: Isolation of song-regulated genes in the brain of songbirds. Methods Mol Biol 85:205–217, 1997
[PubMed]
 
Menalled LB: Knock-in mouse models of Huntington's disease. NeuroRx 2:465–470, 2005
[PubMed]
 
Menalled LB, Sison JD, Wu Y, et al: Early motor dysfunction and striosomal distribution of huntingtin microaggregates in Huntington's disease knock-in mice. J Neurosci 22:8266–8276, 2002
[PubMed]
 
Menalled LB, Sison JD, Dragatsis I, et al: Time course of early motor and neuropathological anomalies in a knock-in mouse model of Huntington's disease with 140 CAG repeats. J Comp Neurol 465:11–26, 2003
[PubMed]
 
Meuer K, Suppanz IE, Lingor P, et al: Cyclin-dependent kinase 5 is an upstream regulator of mitochondrial fission during neuronal apoptosis. Cell Death Differ 14:651–661, 2007
[PubMed]
 
Mizushima K, Miyamoto Y, Tsukahara F, et al: A novel G-protein-coupled receptor gene expressed in striatum. Genomics 69:314–321, 2000
[PubMed]
 
Murata T, Kurokawa R, Krones A, et al: Defect of histone acetyltransferase activity of the nuclear transcriptional coactivator CBP in Rubinstein-Taybi syndrome. Hum Mol Genet 10:1071–1076, 2001
[PubMed]
 
Murphy KP, Carter RJ, Lione LA, et al: Abnormal synaptic plasticity and impaired spatial cognition in mice transgenic for exon 1 of the human Huntington's disease mutation. J Neurosci 20:5115–5123, 2000
[PubMed]
 
Nasir J, Floresco SB, O'Kusky JR, et al: Targeted disruption of the Huntington's disease gene results in embryonic lethality and behavioral and morphological changes in heterozygotes. Cell 81:811–823, 1995
[PubMed]
 
Neve RL: Adenovirus vectors enter the brain. Trends Neurosci 16:251–253, 1993
[PubMed]
 
Nolte C, Matyash M, Pivneva T, et al: GFAP promoter-controlled EGFP-expressing transgenic mice: a tool to visualize astrocytes and astrogliosis in living brain tissue. Glia 33:72–86, 2001
[PubMed]
 
Oike Y, Hata A, Mamiya T, et al: Truncated CBP protein leads to classical Rubinstein-Taybi syndrome phenotypes in mice: implications for a dominant-negative mechanism. Hum Mol Genet 8:387–396, 1999
[PubMed]
 
Osawa S, Johnson GL: A dominant negative G alpha s mutant is rescued by secondary mutation of the alpha chain amino terminus. J Biol Chem 266:4673–4676, 1991
[PubMed]
 
Pai SI, Lin YY, Macaes B, et al: Prospects of RNA interference therapy for cancer. Gene Ther 13:464–477, 2006
[PubMed]
 
Peng S, York JP, Zhang P: A transgenic approach for RNA interference-based genetic screening in mice. Proc Natl Acad Sci U S A 103:2252–2256, 2006
[PubMed]
 
Perou CM, Jeffrey SS, van de Rijn M, et al: Distinctive gene expression patterns in human mammary epithelial cells and breast cancers. Proc Natl Acad Sci U S A 96:9212–9217, 1999
[PubMed]
 
Petrij F, Giles RH, Dauwerse HG, et al: Rubinstein-Taybi syndrome caused by mutations in the transcriptional co-activator CBP. Nature 376:348–351, 1995
[PubMed]
 
Phillips MI, Ambuhl P, Gyurko R: Antisense oligonucleotides for in vivo studies of angiotensin receptors. Adv Exp Med Biol 396:79–92, 1996
[PubMed]
 
Provost P, Silverstein RA, Dishart D, et al: Dicer is required for chromosome segregation and gene silencing in fission yeast cells. Proc Natl Acad Sci U S A 99:16648–16653, 2002
[PubMed]
 
Raoul C, Barker SD, Aebischer P: Viral-based modelling and correction of neurodegenerative diseases by RNA interference. Gene Ther 13:487–495, 2006
[PubMed]
 
Rasenick MM, Watanabe M, Lazarevic MB, et al: Synthetic peptides as probes for G protein function. Carboxyl-terminal G alpha s peptides mimic Gs and evoke high affinity agonist binding to beta-adrenergic receptors. J Biol Chem 269:21519–21525, 1994
[PubMed]
 
Roll-Mecak A, Cao C, Dever TE, et al: X-Ray structures of the universal translation initiation factor IF2/eIF5B: conformational changes on GDP and GTP binding. Cell 103:781–792, 2000
[PubMed]
 
Rossi JJ: RNAi as a treatment for HIV-1 infection. Biotechniques Suppl:25–29, 2006
 
Sanada K, Tsai LH: G protein betagamma subunits and AGS3 control spindle orientation and asymmetric cell fate of cerebral cortical progenitors. Cell 122:119–131, 2005
[PubMed]
 
Scadden AD, Smith CW: Specific cleavage of hyper-edited dsRNAs. Embo J 20:4243–4252, 2001
[PubMed]
 
Schmitz C, Kinge P, Hutter H: Axon guidance genes identified in a large-scale RNAi screen using the RNAi-hypersensitive Caenorhabditis elegans strain nre-1(hd20) lin-15b(hd126). Proc Natl Acad Sci U S A 104:834–839, 2007
[PubMed]
 
Seeburg PH, Hartner J: Regulation of ion channel/neurotransmitter receptor function by RNA editing. Curr Opin Neurobiol 13:279–283, 2003
[PubMed]
 
Setou M, Nakagawa T, Seog DH, et al: Kinesin superfamily motor protein KIF17 and mLin-10 in NMDA receptor-containing vesicle transport. Science 288:1796–1802, 2000
[PubMed]
 
Shaner NC, Campbell RE, Steinbach PA, et al: Improved monomeric red, orange and yellow fluorescent proteins derived from Discosoma sp. red fluorescent protein. Nat Biotechnol 22:1567–1572, 2004
[PubMed]
 
Shaner NC, Steinbach PA, Tsien RY: A guide to choosing fluorescent proteins. Nat Methods 2:905–909, 2005
[PubMed]
 
Shi GX, Rehmann H, Andres DA: A novel cyclic AMP-dependent Epac-Rit signaling pathway contributes to PACAP38-mediated neuronal differentiation. Mol Cell Biol 26:9136–9147, 2006
[PubMed]
 
Shi Y: Mammalian RNAi for the masses. Trends Genet 19:9–12, 2003
[PubMed]
 
Sijen T, Fleenor J, Simmer F, et al: On the role of RNA amplification in dsRNA-triggered gene silencing. Cell 107:465–476, 2001
[PubMed]
 
Simpson L, Emeson RB: RNA editing. Annu Rev Neurosci 19:27–52, 1996
[PubMed]
 
Siolas D, Lerner C, Burchard J, et al: Synthetic shRNAs as potent RNAi triggers. Nat Biotechnol 23:227–231, 2005
[PubMed]
 
Slack RS, Belliveau DJ, Rosenberg M, et al: Adenovirus-mediated gene transfer of the tumor suppressor, p53, induces apoptosis in postmitotic neurons. J Cell Biol 135:1085–1096, 1996
[PubMed]
 
Slow EJ, van Raamsdonk J, Rogers D, et al: Selective striatal neuronal loss in a YAC128 mouse model of Huntington disease. Hum Mol Genet 12:1555–1567, 2003
[PubMed]
 
Starling AJ, Andre VM, Cepeda C, et al: Alterations in N-methyl-D-aspartate receptor sensitivity and magnesium blockade occur early in development in the R6/2 mouse model of Huntington's disease. J Neurosci Res 82:377–386, 2005
[PubMed]
 
Steward O, Wallace CS: mRNA distribution within dendrites: relationship to afferent innervation. J Neurobiol 26:447–449, 1995
[PubMed]
 
Strachan RT, Ferrara G, Roth BL: Screening the receptorome: an efficient approach for drug discovery and target validation. Drug Discov Today 11:708–716, 2006
[PubMed]
 
Strahl BD, Allis CD: The language of covalent histone modifications. Nature 403:41–45, 2000
[PubMed]
 
Stuart K, Panigrahi AK: RNA editing: complexity and complications. Mol Microbiol 45:591–596, 2002
[PubMed]
 
Sturchler-Pierrat C, Abramowski D, Duke M, et al: Two amyloid precursor protein transgenic mouse models with Alzheimer disease-like pathology. Proc Natl Acad Sci U S A 94:13287–13292, 1997
[PubMed]
 
Tahiliani M, Mei P, Fang R, et al: The histone H3K4 demethylase SMCX links REST target genes to X-linked mental retardation. Nature 447:601–605, 2007
[PubMed]
 
Takei Y, Teng J, Harada A, et al: Defects in axonal elongation and neuronal migration in mice with disrupted tau and map 1b genes. J Cell Biol 150:989–1000, 2000
[PubMed]
 
Tanaka S, Kitagawa K, Ohtsuki T, et al: Synergistic induction of HSP40 and HSC70 in the mouse hippocampal neurons after cerebral ischemia and ischemic tolerance in gerbil hippocampus. J Neurosci Res 67:37–47, 2002
[PubMed]
 
Templin MF, Stoll D, Schrenk M, et al: Protein microarray technology. Trends Biotechnol 20:160–166, 2002
[PubMed]
 
Tochitani S, Liang F, Watakabe A, et al: The occ1 gene is preferentially expressed in the primary visual cortex in an activity-dependent manner: a pattern of gene expression related to the cytoarchitectonic area in adult macaque neocortex. Eur J Neurosci 13:297–307, 2001
[PubMed]
 
Tomari Y, Zamore PD: Perspective: machines for RNAi. Genes Dev 19:517–529, 2005
[PubMed]
 
Tsai K, Chen S, Ma Y, et al: sgk, a primary glucocorticoid-induced gene, facilitates memory consolidation of spatial learning in rats. Proc Natl Acad Sci U S A 99:3990–3995, 2002
[PubMed]
 
Valasek MA, Repa JJ: The power of real-time PCR. Adv Physiol Educ 29:151–159, 2005
[PubMed]
 
Venter JC, Adams MD, Yan C, et al: The sequence of the human genome. Science 291:1304–1351, 2001
[PubMed]
 
Volpe TA, Kidner C, Hall IM, et al: Regulation of heterochromatic silencing and histone H3 lysine-9 methylation by RNAi. Science 297:1833–1837, 2002
[PubMed]
 
Wang Q, O'Brien PJ, Chen CX, et al: Altered G protein-coupling functions of RNA editing isoform and splicing variant serotonin2C receptors. J Neurochem 74:1290–1300, 2000
[PubMed]
 
Wang Q, Zhang Z, Blackwell K, et al: Vigilins bind to promiscuously A-to-I-edited RNAs and are involved in the formation of heterochromatin. Curr Biol 15:384–391, 2005
[PubMed]
 
Wedegaertner PB, Bourne HR: Activation and depalmitoylation of Gs alpha. Cell 77:1063–1070, 1994
[PubMed]
 
Whitney LW, Becker KG, Tresser NJ, et al: Analysis of gene expression in multiple sclerosis lesions using cDNA microarrays. Ann Neurol 46:425–428, 1999
[PubMed]
 
Wieden HJ, Gromadski K, Rodnin D, et al: Mechanism of elongation factor (EF)-Ts-catalyzed nucleotide exchange in EF-Tu: contribution of contacts at the guanine base. J Biol Chem 277:6032–6036, 2002
[PubMed]
 
Wittwer CT, Herrmann MG, Moss AA, et al: Continuous fluorescence monitoring of rapid cycle DNA amplification. Biotechniques 22:130–131, 134–138, 1997
 
Xia XG, Zhou H, Xu Z: Promises and challenges in developing RNAi as a research tool and therapy for neurodegenerative diseases. Neurodegener Dis 2:220–231, 2005
[PubMed]
 
Xia X, Zhou H, Huang Y, et al: Allele-specific RNAi selectively silences mutant SOD1 and achieves significant therapeutic benefit in vivo. Neurobiol Dis 23:578–586, 2006
[PubMed]
 
Yamada T, Sakisaka T, Hisata S, et al: RA-RhoGAP, Rap-activated Rho GTPase-activating protein implicated in neurite outgrowth through Rho. J Biol Chem 280:33026–33034, 2005
[PubMed]
 
Yanaka N, Nogusa Y, Fujioka Y, et al: Involvement of membrane protein GDE2 in retinoic acid-induced neurite formation in Neuro2A cells. FEBS Lett 581:712–718, 2007
[PubMed]
 
Yang W, Wang Q, Kanes SJ, et al: Altered RNA editing of serotonin 5-HT2C receptor induced by interferon: implications for depression associated with cytokine therapy. Brain Res Mol Brain Res 124:70–78, 2004
[PubMed]
 
Yano M, Nakamuta S, Shiota M, et al: Gatekeeper role of 14–3–3tau protein in HIV-1 gp120-mediated apoptosis of human endothelial cells by inactivation of Bad. AIDS 21:911–920, 2007
[PubMed]
 
Yu JZ, Rasenick MM: Real-time visualization of a fluorescent G(alpha)(s): dissociation of the activated G protein from plasma membrane. Mol Pharmacol 61:352–359, 2002
[PubMed]
 
Yu JZ, DeRuiter SL, Turner DL: RNA interference by expression of short-interfering RNAs and hairpin RNAs in mammalian cells. Proc Natl Acad Sci U S A 99:6047–6052, 2002a
 
Yu JZ, Kuret J, Rasenick MM: Transient expression of fluorescent tau proteins promotes process formation in PC12 cells: contributions of the tau C-terminus to this process. J Neurosci Res 67:625–633, 2002b
 
Zeitlin S, Liu JP, Chapman DL, et al: Increased apoptosis and early embryonic lethality in mice nullizygous for the Huntington's disease gene homologue. Nat Genet 11:155–163, 1995
[PubMed]
 
Zeng Y, Wagner EJ, Cullen BR: Both natural and designed micro RNAs can inhibit the expression of cognate mRNAs when expressed in human cells. Mol Cell 9:1327–1333, 2002
[PubMed]
 
Zhang Z, Carmichael GG: The fate of dsRNA in the nucleus: a p54(nrb)-containing complex mediates the nuclear retention of promiscuously A-to-I edited RNAs. Cell 106:465–475, 2001
[PubMed]
 
Zhang Z, Yang X, Zhang S, et al: BNIP3 upregulation and EndoG translocation in delayed neuronal death in stroke and in hypoxia. Stroke 38:1606–1613, 2007
[PubMed]
 
Zhou H, Falkenburger BH, Schulz JB, et al: Silencing of the Pink1 gene expression by conditional RNAi does not induce dopaminergic neuron death in mice. Int J Biol Sci 3:242–250, 2007
[PubMed]
 
Zhu H, Klemic JF, Chang S, et al: Analysis of yeast protein kinases using protein chips. Nat Genet 26:283–289, 2000
[PubMed]
 
Zhu H, Bilgin M, Bangham R, et al: Global analysis of protein activities using proteome chips. Science 293:2101–2105, 2001
[PubMed]
 
+

CME Activity

Add a subscription to complete this activity and earn CME credit.
Sample questions:
1.
As a result of the sequencing of all of the human genome, the number of human genes was estimated to be
2.
Genes undergo a process in which an RNA molecule complementary to one of the gene’s DNA strands is synthesized using nucleotide triphosphates. What is this process called?
3.
A rapid procedure for in vitro enzymatic amplification of specific segments of DNA is called
NOTE:
Citing articles are presented as examples only. In non-demo SCM6 implementation, integration with CrossRef’s "Cited By" API will populate this tab (http://www.crossref.org/citedby.html).
Related Content
Articles
Books
The American Psychiatric Publishing Textbook of Psychopharmacology, 4th Edition > Chapter 3.  >
Topic Collections
Psychiatric News
PubMed Articles
In-Depth Transcriptome Analysis of the Red Swamp Crayfish Procambarus clarkii. PLoS One 2014;9(10):e110548.doi:10.1371/journal.pone.0110548.
 
  • Print
  • PDF
  • E-mail
  • Chapter Alerts
  • Get Citation