ALKBH5-induced demethylation of mono- and dimethylated adenosine

Timm T Ensfelder1, Matthias Q Kurz1, Katharina Iwan1

  • 1Center for Integrated Protein Science, Department of Chemistry, Ludwig-Maximilians-Universität München, Butenandtstraße 5-13, 81377 Munich, Germany. Thomas.carell@lmu.de.

Chemical Communications (Cambridge, England)
|July 17, 2018
PubMed

Insights

The enzyme ALKBH5, known for removing methyl groups from messenger RNA (mRNA), also demethylates a different modified base, dimethylated adenosine (m62A), found in ribosomal RNA (rRNA). This expands our understanding of RNA base modification regulation.

Area of Science:

  • Biochemistry
  • Molecular Biology
  • RNA Biology

Background:

  • RNA modifications, such as N6-methyladenosine (m6A), play crucial roles in regulating gene expression and cellular homeostasis.
  • Demethylation of m6A is primarily attributed to the α-ketoglutarate-dependent oxidase ALKBH5.
  • Dimethylated adenosine (m62A) is a non-canonical base modification found in ribosomal RNA (rRNA).

Purpose of the Study:

  • To investigate the enzymatic activity of ALKBH5 beyond its known role in m6A demethylation.
  • To determine if ALKBH5 can act on other methylated adenosine derivatives, specifically m62A in rRNA.

Main Methods:

  • Biochemical assays to test ALKBH5 activity on synthetic RNA substrates containing m62A.
  • Analysis of ALKBH5's interaction with rRNA.
  • In vitro demethylation assays.

Main Results:

  • ALKBH5 demonstrates demethylase activity on dimethylated adenosine (m62A).
  • ALKBH5 is capable of removing the methyl groups from m62A in ribosomal RNA.
  • This finding reveals a novel function for ALKBH5 in regulating rRNA modifications.

Conclusions:

  • ALKBH5 possesses a broader substrate specificity than previously recognized, acting on both m6A and m62A.
  • The enzyme plays a role in the homeostasis of both mRNA and rRNA modifications.
  • This discovery opens new avenues for research into RNA base modification dynamics and their regulatory roles.

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