The   synthesis   of   new   ribosomes   is   critical   for   the   survival   of   all   organisms.   In the   early   1960s,   Nomura   and   colleagues   found   30S   ribosomal   subunits   can   be assembled   in   vitro,   and   the   assembly   is   highly   cooperative   and   hierarchical. Since   then,   thermodynamics   and   kinetics   of   protein   addition,   RNA   folding during   ribosomal   assembly,   and   the   structural   basis   for   cooperative   protein addition   have   been   studied   extensively.   In   addition   to   r-proteins,   various   other assembly   factors   and   nucleotide   modification   enzymes   are   involved   in   the ribosomal   assembly.   Interestingly,   in   vivo,   both   ribosomal   assembly   and   rRNA modifications   occur   co-transcriptionally.   However,   less   is   known   about   these nucleotide   modification   steps   and   how   these   steps   are   integrated   into   the mechanism   of   ribosomal   protein   addition.   Nucleotide   modification   steps   of rRNA   can   influence   the   ribosomal   assembly   in   two   separate   ways.      First,   post- transcriptional   modifications   can   perturb   local   RNA   structure,   stability,   and dynamics    hence    modulating    RNA    folding.    Similarly,    modified    nucleotides provide    additional    hydrophobic    patches    that    will    change    the    affinity    of ribosomal      proteins.      Secondly,      thermodynamic      cooperativity      between modification    enzymes    and    r-proteins    generates    low-energy    pathways    for assembly   to   proceed.   Conversely,   kinetic   cooperativity   between   modification enzymes    and    r-proteins    can    prevent    the    formation    of    undesirable    and unproductive      assembly      intermediates.      In      our      lab,      we      investigate thermodynamic   and   kinetic   cooperativity   of   binding   between   rRNA   modification enzyme and r-proteins. read more...