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  <head>
    <title>091-02 Transcription, RNA processing, noncoding RNA, and post-transcriptional control</title>
    <ownerName>Integrated Medical Foundations</ownerName>
  </head>
  <body>
    <outline text="Transcription and RNA control">
      <outline text="RNA roles and polymerases">
        <outline text="RNA is catalyst, scaffold, guide, regulator"/>
        <outline text="Polymerase one: most ribosomal RNA"/>
        <outline text="Polymerase two: messenger and many noncoding RNAs"/>
        <outline text="Polymerase three: transfer, 5S, small RNAs"/>
        <outline text="Template read 3&#x27; to 5&#x27;, RNA made 5&#x27; to 3&#x27;"/>
      </outline>
      <outline text="Initiation and elongation">
        <outline text="Activators, general factors, mediator assemble"/>
        <outline text="Not every promoter has a TATA box"/>
        <outline text="Carboxyl-terminal domain phosphorylation">
          <outline text="Escape into elongation"/>
          <outline text="Recruits RNA-processing factors"/>
        </outline>
        <outline text="Enhancers act at distance, either orientation">
          <outline text="Silencers and insulators constrain"/>
          <outline text="Noncoding variants alter quantity, timing, place"/>
        </outline>
        <outline text="Elongation meets nucleosomes and supercoiling"/>
        <outline text="Promoter-proximal pausing keeps genes poised"/>
        <outline text="Transcription rate shapes splicing choice"/>
      </outline>
      <outline text="Capping and splicing">
        <outline text="Seven-methylguanosine cap, 5&#x27;-5&#x27; bond">
          <outline text="Protects, recruits export, supports translation"/>
        </outline>
        <outline text="snRNPs recognise splice sites and branch point"/>
        <outline text="Two transesterifications form a lariat">
          <outline text="No direct ATP for bond chemistry"/>
        </outline>
        <outline text="Alternative splicing expands diversity">
          <outline text="Prominent in brain, muscle, development"/>
        </outline>
        <outline text="Splicing variants">
          <outline text="Synonymous change can be pathogenic"/>
          <outline text="Deep intronic variants create pseudoexons"/>
          <outline text="Relevant tissue RNA, blood may lack it"/>
        </outline>
      </outline>
      <outline text="Three-prime end, export, and localisation">
        <outline text="Cleavage and poly-A tail addition"/>
        <outline text="Alternative polyadenylation">
          <outline text="Changes microRNA sites, localisation, product"/>
        </outline>
        <outline text="Histone messenger RNAs non-polyadenylated"/>
        <outline text="Quality-checked export through nuclear pores">
          <outline text="Faulty transcripts degraded by nuclear exosome"/>
        </outline>
        <outline text="Local translation in dendrites and axons"/>
      </outline>
      <outline text="Decay and surveillance">
        <outline text="Deadenylation starts decay">
          <outline text="Decapping and exonuclease, or exosome"/>
        </outline>
        <outline text="AU-rich elements tune inflammatory transcripts"/>
        <outline text="Stability changes act faster than transcription"/>
        <outline text="Nonsense-mediated decay">
          <outline text="Loss through RNA degradation"/>
          <outline text="Escape gives dominant-negative products"/>
        </outline>
        <outline text="Nonstop, no-go, ribosome quality control">
          <outline text="Neurons especially vulnerable"/>
        </outline>
      </outline>
      <outline text="Editing and chemical modification">
        <outline text="Adenosine-to-inosine editing by ADAR">
          <outline text="Inosine read as guanosine"/>
        </outline>
        <outline text="Cytidine editing: apolipoprotein B48"/>
        <outline text="Editing is not genomic mutation"/>
        <outline text="N6-methyladenosine writers and readers"/>
        <outline text="Epitranscriptome mapping needs careful controls"/>
      </outline>
      <outline text="Small regulatory RNAs">
        <outline text="MicroRNAs processed by Drosha and Dicer">
          <outline text="Seed pairing lowers translation or stability"/>
          <outline text="Many modest targets per microRNA"/>
        </outline>
        <outline text="Small interfering RNAs: extensive pairing, cleavage">
          <outline text="Delivery, off-target, immune limits"/>
          <outline text="Does not alter genomic DNA"/>
        </outline>
      </outline>
      <outline text="Long, circular, and structural RNAs">
        <outline text="Long noncoding RNAs over about 200 nucleotides">
          <outline text="XIST initiates dosage compensation"/>
          <outline text="Expression alone does not prove function"/>
        </outline>
        <outline text="Circular RNAs from back-splicing"/>
        <outline text="Small nucleolar RNAs guide rRNA modification"/>
        <outline text="Membraneless condensates">
          <outline text="Stress granules sequester translation parts"/>
          <outline text="Processing bodies hold decay factors"/>
        </outline>
      </outline>
      <outline text="Interpretation, measurement, and therapy">
        <outline text="One gene, many outputs">
          <outline text="Identify the tissue-relevant transcript"/>
        </outline>
        <outline text="Measurement methods carry biases">
          <outline text="RNA level is not protein level"/>
        </outline>
        <outline text="Antisense, interfering, messenger, guide RNA therapies">
          <outline text="Modification and delivery improve targeting"/>
        </outline>
        <outline text="Normal coding sequence is not normal expression"/>
      </outline>
    </outline>
  </body>
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