SUB-NUCLEAR STRUCTURES

SUB-NUCLEAR STRUCTURES

1. NUCLEOLUS

   • Consists of 3 components
     • dense fibrillar components
     • fibrillar components
     • granular components
   • ribosome biogenesis
     • 1) rRNAs are transcribed into long precursor pre-mRNA molecules by RNA Pol 1 and II and pol-associated factors
       • 2) the precursors are further modified to produce 5S, 5.5S, 18S and 28S RNA molecules
         • 3) RNA modifying enzymes are brought to rRNAs by guide RNAs and snoRNAs which are complexed with snoRNPs
           • Pnce processed, they are assembled to form large ribosomal subunits and ribosomal proteins
             • rRNAs and r-proteins undergo association and maturation to produce 40S and 60S subunits
   • RIBOSOMOPATHIES
     • A group of genetic disorders where genetic abnormalites causes impaired ribosomal biogenesis resulting in clinical phenotypes
       • Diamond BlackFan Anaemia (DBA)
         • LOW RBC due to mutation in ribsomal subunit S19
           • congential abnormalities
       • Treacher-Collins Syndrome (TCS)
         • mutation in TCO1 gene that encodes for Treacle
           • causes craniofacial abnormalities
   • largest non-membrane bound structure
     • mainly consists of nucleic acid and proteins

2. CAJAL BODIES

   • Involved in maturation and assembly of snRNPs and snoRNPs
     • DISEASE IN CB AND NG
       • Spinal muscular Atrophy
         • caused by mutation in SMN1 gene that encodes for SMN
           • SMN involved in ribosome biogenesis
             • causes splicing defects

3. NUCLEAR GEMS

   • contain SMN protein which is involved in ribosome biogenesis

4. NUCLEAR SPECKLES

   • Storage and modification compartment for pre-mRNA splicing factors including snRNPs and SR proteins
     • DISEASE- retinitis pigmentosa
       • where vision turns from night blindness -> tunnel vision -> complete blindness
         • mutation linked to splicing factors

5. POLYCOMB BODIES

   • Hub for gene repression
   • PcGs
     • remodels chromatin including epigenetic splicing
     • directly binds to DNA complexes and facilitate recruitment of other complexes
     • PML bodies
       • dynamic bodies facilitating the release of proteins and mediating post-transcriptional modifications
       • DISEASE - acute promeolytic leukaemia