Dynamic RNA modifications in disease.

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.

Klungland A ，Dahl JA 《-》

Preparation of Human Nuclear RNA m⁶A Methyltransferases and Demethylases and Biochemical Characterization of Their Catalytic Activity.

N(6)-Methyladenosine (m(6)A) represents the most prevalent internal modification in messenger and long noncoding RNAs. There has been a surge of interest toward understanding the biological significance of m(6)A modification. In this chapter, we describe the methods for biochemically studying the recently uncovered m(6)A methyltransferases (METTL3 and METTL14) and demethylases (FTO and ALKBH5). How to express these proteins, perform their biochemistry reactions against various RNA probes, and characterize the methylation and demethylation activity will be discussed.

Liu J ，Yue Y ，He C 《-》

Decreased N(6)-methyladenosine in peripheral blood RNA from diabetic patients is associated with FTO expression rather than ALKBH5.

Shen F ，Huang W ，Huang JT ，Xiong J ，Yang Y ，Wu K ，Jia GF ，Chen J ，Feng YQ ，Yuan BF ，Liu SM ... -  《-》

The dynamic epitranscriptome: N6-methyladenosine and gene expression control.

Meyer KD ，Jaffrey SR 《-》

METTL3 and ALKBH5 oppositely regulate m(6)A modification of TFEB mRNA, which dictates the fate of hypoxia/reoxygenation-treated cardiomyocytes.

Song H ，Feng X ，Zhang H ，Luo Y ，Huang J ，Lin M ，Jin J ，Ding X ，Wu S ，Huang H ，Yu T ，Zhang M ，Hong H ，Yao S ，Zhao Y ，Zhang Z ... -  《-》