microRNAs决定哺乳动物的基因进化(2)

But  while  Grimson  showed  that,  at  least  in  the  lab,  microRNAs  could  regulate  mRNAs  with  nonconserved  sites,  the  researchers  still  didn't  know  the  extent  to  which  nonconserved  mRNAs  coexisted  with  their  matching  microRNAs  in  the  natural  cell  environment.  To  answer  this  question,  the  researchers  turned  to  gene  expression  patterns  of  different  types  of  mouse  cells.

Kyle  Kai-How  Farh,  a  graduate  student  in  Bartel's  lab,  found  that  mRNAs  with  nonconserved  sites  were  generally  absent  in  cells  with  corresponding  microRNAs--more  absent  than  statistical  models  suggested.  The  researchers  concluded  that  over  the  course  of  evolution  many  mRNAs,  in  order  to  maintain  their  functions  and  ensure  fitness  of  the  organism,  have  quickly  lost  sites  that  pair  up  with  microRNAs.

In  addition  to  the  thousands  of  cases  where  genes  have  avoided  microRNA  targeting,  Farh  also  investigated  the  opposite  extreme,  cases  where  genes  have  maintained  microRNA  target  sites  over  the  course  of  evolution.  He  found  that  as  immature  muscle  cells  stop  dividing  and  become  mature  muscle  cells,  microRNAs  are  activated  and  suppress  genes  that  are  no  longer  needed  at  such  high  levels  in  the  mature  muscle.  "Many  of  these  evolutionarily  conserved  microRNA  targets  are  known  to  be  active  in  the  processes  of  cell  proliferation,  development,  and  cancer,"  says  Farh.  "Our  genomes  have  good  reason  to  maintain  the  microRNA  targeting  sites  necessary  for  turning  down  these  genes  at  the  appropriate  place  and  time."

An  emerging  idea  is  that  microRNAs  often  act  to  reduce  the  quantity  of  protein  a  gene  produces  without  shutting  it  off  all  together.  "We  think  the  microRNAs  are  sometimes  having  what  you  can  call  a  dampening  effect,"  says  Bartel,  who  is  also  a  Howard  Hughes  Medical  Institute  investigator  and  MIT  professor  of  biology.  "They  appear  to  be  helping  cells  achieve  optimal  levels  of  proteins."   (责任编辑：泉水)

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microRNAs决定哺乳动物的基因进化(2)