SUB-NUCLEAR STRUCTURES

SUB-NUCLEAR STRUCTURES

1. NUCELOLUS

   • Largest non-membrane structure in nucleus mainly composing of proteins and nucleic acids
     • ribosome biogenesis
       • rRNAs are transcribed by RNA pol I and II and several pol-associated factors to form a long precursor 45S pre-mRNA subunit
         • the precursor molecule is further processed to form 5s, 5.8S. 18S and 28S RNA molecule
           • RNA modifying enzymes brought to rRNAs by interactions with guide RNAs and snoRNAs with interactions with snoRNPs
             • once processed, they are assembled into large ribosomal subunits with ribosomal sununits
               • Association and maturation of rRNAs and r-proteins results in formation of 40s and 60s large subunits
     • 3 major components
       • fibrillar components
       • granular components
       • dense fibrillar components
     • DISEASE: Ribsomopathies
       • collection of disorders caused by genetic abnormalities in impaired ribosome biognesis and function that cause specific clinical phenotypes
         • Diamond Blackfan anaemia (DBA)
           • mutation in ribosome S19- Low RBC count causing congenital abnormalities
         • Treacher-collins syndrome (TCS)
           • mutations in TCOP1 gene causing low RBC -cranofacial abnormalities

2. cajal bodies

   • involved in maturation and assembly of snRNPs and sno RNPs
     • DISEASE: Spinal muscular Atrophy
       • causes mutation in SMN1 gene that encodes for SMN gene
         • SMN gene is involved in snRNP assembly -mutation causes splicing defects

3. Nuclear gems

   • contains SMN genes which is involved in snRNP biogenesis

4. nuclear speckles

   • storage and modification compartment for pre-mRNA splicing factors including snoRNPs and SR proteins
   • DIESASE: retinitis pigmentosa

5. POLYCOMB BODIES

   • Hub for gene repression and usually associated with heterochromatin
   • PCGs
     • remodels chromatin including in epigenetic silencing
     • directly binds to specific DNA sequences to facilitate and recruit other DNA complexes

6. PML BODIES

   • dynamic structures favouring the release of protein and mediating their post-translational modification
   • DISEASE: acute promyeolytic leukaemia