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RNA methyltransferase METTL16: Targets and function.

Emily R Satterwhite1, Kyle D Mansfield1

  • 1Department of Biochemistry and Molecular Biology, Brody School of Medicine, East Carolina University, Greenville, North Carolina, USA.

Wiley Interdisciplinary Reviews. RNA
|July 6, 2021
PubMed
Summary

The N6-methyladenosine (m6A) RNA methyltransferase METTL16 is essential for human cells, methylating key RNAs like MAT2A mRNA and U6 snRNA. Its precise roles in RNA splicing and cellular survival are under active investigation.

Keywords:
METTL16N6-methyladenosineRNA bindingRNA methyltransferaseepitranscriptomics

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Area of Science:

  • Molecular Biology
  • RNA Biology
  • Epigenetics

Background:

  • N6-methyladenosine (m6A) RNA methyltransferase METTL16 is a critical regulator in human cells.
  • Initially identified as a ribosomal RNA methyltransferase, its functions have expanded to include methylation of messenger RNA (mRNA) and small nuclear RNA (snRNA).

Purpose of the Study:

  • To elucidate the multifaceted roles of METTL16 in RNA modification and cellular processes.
  • To investigate METTL16's interactions with MAT2A mRNA, U6 snRNA, MALAT1 long noncoding RNA, and other RNA species.
  • To understand the structural and functional significance of METTL16's methyltransferase and RNA-binding domains.

Main Methods:

  • Characterization of METTL16's methyltransferase activity using S-adenosylmethionine (SAM) as a methyl donor.
  • Identification of RNA methylation consensus sequences (UACAGARAA) and structural requirements for RNA interactors.
  • Analysis of METTL16's protein domains, including the methyltransferase domain, RNA binding domains, and nuclear localization signal.

Main Results:

  • METTL16 binds and methylates MAT2A mRNA and U6 snRNA, and also interacts with MALAT1 lncRNA.
  • The protein possesses a class I methyltransferase fold and specific RNA interaction motifs.
  • Evidence suggests METTL16 is essential for cell viability, potentially through regulating MAT2A mRNA splicing in response to SAM levels.

Conclusions:

  • METTL16 is a crucial RNA binding protein and methyltransferase with emerging roles in RNA processing and cellular regulation.
  • Further research is needed to fully understand the impact of U6 snRNA methylation by METTL16 on splicing and cell survival.
  • The complete repertoire of METTL16's RNA interactors and their functional significance remains an active area of investigation.