Dynamic RNA modifications in disease

Curr Opin Genet Dev. 2014 Jun:26:47-52. doi: 10.1016/j.gde.2014.05.006. Epub 2014 Jul 5.

Abstract

While the presence of 6-methyladenosine (m6A) modifications in mRNA was noted several decades ago, the first enzyme reversing this modification was identified very recently. Today we know of two methyltransferases introducing m6A in mRNA--METTL3 and METTL14--and two demethylases that remove it have been identified-FTO (ALKBH9) and ALKBH5. The conserved role of m6A seems to relate to meiosis, and mice lacking ALKBH5 are infertile. While loss-of-function mutation in FTO causes a recessive lethal syndrome, sequence variants in introns of the FTO gene are associated with obesity and type 2 diabetes.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Adenosine / analogs & derivatives*
  • Adenosine / metabolism
  • AlkB Homolog 5, RNA Demethylase
  • Alpha-Ketoglutarate-Dependent Dioxygenase FTO
  • Diabetes Mellitus, Type 2 / genetics
  • Diabetes Mellitus, Type 2 / metabolism*
  • Dioxygenases / genetics
  • Dioxygenases / metabolism
  • Humans
  • Membrane Proteins / genetics
  • Membrane Proteins / metabolism
  • Methyltransferases / genetics
  • Methyltransferases / metabolism
  • Mutation
  • Obesity / genetics
  • Obesity / metabolism*
  • Proteins / genetics
  • Proteins / metabolism
  • RNA, Messenger / genetics
  • RNA, Messenger / metabolism*

Substances

  • Membrane Proteins
  • Proteins
  • RNA, Messenger
  • N-methyladenosine
  • Dioxygenases
  • ALKBH5 protein, human
  • AlkB Homolog 5, RNA Demethylase
  • Alpha-Ketoglutarate-Dependent Dioxygenase FTO
  • FTO protein, human
  • METTL14 protein, human
  • Methyltransferases
  • METTL3 protein, human
  • Adenosine