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42          SECTION II    BIOCHEmISTRY  ``BIOCHEMISTRY—MOlECUlAR                                                                                                     BIOCHEmISTRY  ``BIOCHEMISTRY—MOlECUlAR





               RNA polymerases
                Eukaryotes           RNA polymerase I makes rRNA, the most     I, II, and III are numbered in the same order
                                       common (rampant) type; present only in   that their products are used in protein
                                       nucleolus.                               synthesis: rRNA, mRNA, then tRNA.
                                     RNA polymerase II makes mRNA (massive),   α-amanitin, found in Amanita phalloides (death
                                       microRNA (miRNA), and small nuclear RNA   cap mushrooms), inhibits RNA polymerase II.
                                      (snRNA).                                  Causes severe hepatotoxicity if ingested.
                                     RNA polymerase III makes 5S rRNA, tRNA    Actinomycin D, also called dactinomycin,
                                      (tiny).                                   inhibits RNA polymerase in both prokaryotes
                                     No proofreading function, but can initiate   and eukaryotes.
                                      chains. RNA polymerase II opens DNA at
                                      promoter site.
                Prokaryotes          1 RNA polymerase (multisubunit complex)   Rifampin inhibits DNA-dependent RNA
                                      makes all 3 kinds of RNA.                 polymerase in prokaryotes.



               Splicing of pre-mRNA  Part of process by which precursor mRNA (pre-mRNA) is transformed into mature mRNA.
                                      Alterations in snRNP assembly can cause clinical disease; eg, in spinal muscular atrophy, snRNP
                                      assembly is affected due to  SMN protein Ž congenital degeneration of anterior horns of spinal
                                      cord Ž symmetric weakness (hypotonia, or “floppy baby syndrome”).


                        Primary transcript combines with  5 splice site  U1 snRNP  Branch point    3 splice site
                        small nuclear ribonucleoproteins
                        (snRNPs) and other proteins to                             U2 snRNP
                        form spliceosome.      5          O  P  GU              A      AG  P  O         3
                                                  Exon 1                 Intron                  Exon 2


                                                                        Spliceosome


                        Cleavage at 5  splice site; lariat-
                        shaped (loop) intermediate is
                        generated.
                                                                       U G
                                                                           P A
                                                                      OH 3    AG  P  O
                                                              Exon 1                   Exon 2





                                                       Mature mRNA
                        Cleavage at 3  splice site; lariat
                        is released to precisely remove    P                  +
                        intron and join 2 exons.   Exon 1        Exon 2                  U G
                                                                                            P A
                                                                                                    AG  OH 3






















          FAS1_2019_01-Biochem.indd   42                                                                                11/7/19   3:16 PM
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