Precursor mRNA

In addition to the weU-defined opioid systems in the central nervous system, the three opioid peptides and their precursor mRNA have also been identified in peripheral tissues. ( -Endorphin is most abundant in the pituitary, where it exists in corticotroph cells with ACTH in the anterior lobe and in melanotroph cells with MSH in the intermediate lobe (59). Enkephalin and pre-pro-enkephalin mRNA have been identified in the adrenal medulla (60) and this has been the source of material for many studies of pro-enkephalin synthesis and regulation. Pre-pro-enkephalin mRNA has also been identified in the anterior and posterior lobes of the pituitary (61). mRNA for all three opioid precursors has been identified in the reproductive system (62—64). POMC... 

Spliceosome The macromolecular complex responsible for precursor mRNA splicing. The spliceosome consists of at least five small nuclear RNAs (snRNA Ul, U2, U4, U5, and U6) and many proteins. 

Opioid receptors and their precursor mRNAs are distributed throughout the brain and spinal cord. High levels of opioid binding have been found in the ascending pathways for nociceptive transmission, including the... 

Golden RN, Morris JE, Sack DA Combined lithium-tricyclic treatment of obsessive-compulsive disorder. Biol Psychiatry 23 181-185, 1988 Goldenberg G, Lang W, Podreka 1, et al Are cognitive deficits in Parkinson s disease caused by frontal lobe dysfunction Journal of Psychophysiology 4 137-144, 1990 Goldgaber D, Harris HW, Hla T Interleukin-1 regulates synthesis of amyloid beta-protein precursor mRNA in human endothelial cells. Proc Natl Acad Sci U S A 86 7606-7610, 1989... 

One of the early demonstrations of sequence removal resulted from the finding that mouse /3-globin precursor mRNA did not form a perfect hybrid with DNA complementary to mature mRNA. When the hybrid was observed with an electron microscope, a loop in the DNA of the heteroduplex appeared, which suggested that the precursor contained internal sequences not present in the mature mRNA (fig. 28.18). These noncoding intervening sequences (introns) are interspersed with coding sequences (exons). 

Heritable and spontaneous genetic disorders represent additional applications for therapeutic ribozymes targeting cellular genes. These include the beta-amyloid peptide precursor mRNA involved in Alzheimer s disease (Currie et al., 1997 Dolzhanskaya et al., 2000), and an autosomal-dominant point mutation in the rhodopsin mRNA that gives rise to photoreceptor degeneration and retinitis pigmentosa (Hauswirth and Lewin, 2000 LaVail et al., 2000). 

Introns are non-coding sequences that are excised from the precursor mRNA by specific cleavage in a process known as splicing. It has been postulated that the presence of introns enhances the efficiency of transcription by stabilizing the RNA structure, and that splicing increases the... 

Sandbrink R, Masters CL, Beyreuther K. Beta A4-amyloid protein precursor mRNA isoforms without exon 15 are ubiquitously expressed in rat tissues including brain, but not in neurons. J Biol Chem 1994 269(2) 1510—1517. 

Four forms of Gs-a subunits of 395, 394, 380 and 379 amino acids have been identified (Fig. 8 and Table III Refs. 15, 177 and 17, and Mattera and Birnbaumer, unpublished). The differences appear to be due to alternate splicing of a common precursor mRNA resulting in insertion/deletion of a block of 45 and 3 nucleotides... 

Tanzi RE, McClatchey AI, Lamperti ED, Villa-Komaroff L, Gusella JF, Neve RL (1988) Protease inhibitor domain encoded by an amyloid protein precursor mRNA associated with Alzheimer s disease. Nature 331 528-530... 

Goldgaber D, Hanis H, Hla T, Maciag T, Dorrrrelly R, Jacobsen J, Vitek M, Gajdusek D (1989) IL-1 regulates syrrtlresis of amyloid beta-proteirr precursor mRNA irr humarr errdotlrelial cells. Proc Natl Acad Sci USA 86 760 7610. 

Postranscriptionai regulation may be accomplished by controlling the rate of precursor mRNA spUcing of TNF [3 and message stability of both TNFa and TNF. ... 

Seiwert, S.D., and Stuart, K. RNA editing Transfer of genetic information from gRNA to precursor mRNA in vitro. Science 266 114-117, 1994. 

Jamison, S.F. and Garcia, B.M. (1992). An ATP-independent U2 small nuclear ribonucleoprotein particle/precursor mRNA complex requires both splice sites and the polypyrimidine tract. Proc. Natl. Acad. Sci. USA 89, 5482-5486. 

Eukaryotic Precursor mRNAs Are Processed to Form Functional mRNAs... 

In prokaryotic cells, which have no nuclei, translation of an mRNA into protein can begin from the 5 end of the mRNA even while the 3 end is still being synthesized by RNA polymerase. In other words, transcription and translation can occur concurrently in prokaryotes. In eukaryotic cells, however, not only is the nucleus separated from the cytoplasm where translation occurs, but also the primary transcripts of protein-coding genes are precursor mRNAs (pre-mRNAs) that must undergo several modifications, collectively termed RNA processing, to yield a functional mRNA (see Figure... 

Quon, D., Catalano, R. and Cordell, B. (1990) Fibrobalst growth factor induces b-amyloid precursor mRNA in glial but not neuronal cultured cells. Biochem. Biophys. Res. Commun. 167 96-102. 

K. Nakayama, H. Ohkubo, T. Hirose, S. Inayama, S. Nakanishi, mRNA sequence for human cardiodilatin-atrial natriuretic factor and regulation of precursor mRNA in rat atria. Nature (Lond.) 310 699-701 (1984) S. Oikawa, M. Imai, A. Ueno, S. Tanaka, T. Noguchi, H. Nakazato, K. Kangawa, A. Fukuda, H. Matsuo, Cloning and -sequence analysis of cDNA encoding a precursor for human atrial natriuretic polypeptides, ibid. 309 724-726 (1984)... 

Fibronectin A family of closely related adhesion glycoproteins, Mj 200,000-250,000, which arise by the alternative splicing of the precursor mRNA. F. is found both as a cell surface protein of the extracellular matrix (also known as Cell Surface Protein, Galac-toprotein A, Large External Transformation Sensitive Protein, Surface Fibroblast Antigen, and Zeta or Z Protein), and in plasma. Plasma fibronectin is incorporated into fibrin clots and is cross-linked to the fibrin, probably via a Gln-Lys transamidation reaction. 

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