Structural insights into mechanisms of the small RNA methyltransferase HEN1

Huang, Ying; Ji, Lijuan; Huang, Qichen; Vassylyev, Dmitry G; Chen, Xuemei; Ma, Jin-Biao

doi:10.1038/nature08433

Title: Structural insights into mechanisms of the small RNA methyltransferase HEN1

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Abstract

RNA silencing is a conserved regulatory mechanism in fungi, plants and animals that regulates gene expression and defence against viruses and transgenes. Small silencing RNAs of {approx}20-30 nucleotides and their associated effector proteins, the Argonaute family proteins, are the central components in RNA silencing. A subset of small RNAs, such as microRNAs and small interfering RNAs (siRNAs) in plants, Piwi-interacting RNAs in animals and siRNAs in Drosophila, requires an additional crucial step for their maturation; that is, 2'-O-methylation on the 3' terminal nucleotide. A conserved S-adenosyl-L-methionine-dependent RNA methyltransferase, HUA ENHANCER 1 (HEN1), and its homologues are responsible for this specific modification. Here we report the 3.1 {angstrom} crystal structure of full-length HEN1 from Arabidopsis in complex with a 22-nucleotide small RNA duplex and cofactor product S-adenosyl-L-homocysteine. Highly cooperative recognition of the small RNA substrate by multiple RNA binding domains and the methyltransferase domain in HEN1 measures the length of the RNA duplex and determines the substrate specificity. Metal ion coordination by both 2' and 3' hydroxyls on the 3'-terminal nucleotide and four invariant residues in the active site of the methyltransferase domain suggests a novel Mg{sup 2+}-dependent 2'-O-methylation mechanism.

Authors:: Huang, Ying; Ji, Lijuan; Huang, Qichen; Vassylyev, Dmitry G; Chen, Xuemei; Ma, Jin-Biao

Publication Date:: Mon Feb 22 00:00:00 EST 2010

Research Org.:: Argonne National Lab. (ANL), Argonne, IL (United States)

Sponsoring Org.:: USDOE

OSTI Identifier:: 1005953

Resource Type:: Journal Article

Journal Name:: Nature

Additional Journal Information:: Journal Volume: 461; Journal Issue: 10, 2009

Country of Publication:: United States

Language:: ENGLISH

Subject:: 36 MATERIALS SCIENCE; ANIMALS; ARABIDOPSIS; CRYSTAL STRUCTURE; DROSOPHILA; FUNGI; GENES; NUCLEOTIDES; PROTEINS; RESIDUES; RNA; SPECIFICITY; SUBSTRATES; VIRUSES

Citation Formats


                    Huang, Ying, Ji, Lijuan, Huang, Qichen, Vassylyev, Dmitry G, Chen, Xuemei, Ma, Jin-Biao, UAB), and UCR). Structural insights into mechanisms of the small RNA methyltransferase HEN1.  United States: N. p., 2010. 
        Web.  doi:10.1038/nature08433.

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                    Huang, Ying, Ji, Lijuan, Huang, Qichen, Vassylyev, Dmitry G, Chen, Xuemei, Ma, Jin-Biao, UAB), & UCR). Structural insights into mechanisms of the small RNA methyltransferase HEN1.  United States.  https://doi.org/10.1038/nature08433

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                    Huang, Ying, Ji, Lijuan, Huang, Qichen, Vassylyev, Dmitry G, Chen, Xuemei, Ma, Jin-Biao, UAB), and UCR). 2010.  
        "Structural insights into mechanisms of the small RNA methyltransferase HEN1".  United States.  https://doi.org/10.1038/nature08433.

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@article{osti_1005953,

  title        = {Structural insights into mechanisms of the small RNA methyltransferase HEN1},

  author       = {Huang, Ying and Ji, Lijuan and Huang, Qichen and Vassylyev, Dmitry G and Chen, Xuemei and Ma, Jin-Biao and UAB) and UCR)},

  abstractNote = {RNA silencing is a conserved regulatory mechanism in fungi, plants and animals that regulates gene expression and defence against viruses and transgenes. Small silencing RNAs of {approx}20-30 nucleotides and their associated effector proteins, the Argonaute family proteins, are the central components in RNA silencing. A subset of small RNAs, such as microRNAs and small interfering RNAs (siRNAs) in plants, Piwi-interacting RNAs in animals and siRNAs in Drosophila, requires an additional crucial step for their maturation; that is, 2'-O-methylation on the 3' terminal nucleotide. A conserved S-adenosyl-L-methionine-dependent RNA methyltransferase, HUA ENHANCER 1 (HEN1), and its homologues are responsible for this specific modification. Here we report the 3.1 {angstrom} crystal structure of full-length HEN1 from Arabidopsis in complex with a 22-nucleotide small RNA duplex and cofactor product S-adenosyl-L-homocysteine. Highly cooperative recognition of the small RNA substrate by multiple RNA binding domains and the methyltransferase domain in HEN1 measures the length of the RNA duplex and determines the substrate specificity. Metal ion coordination by both 2' and 3' hydroxyls on the 3'-terminal nucleotide and four invariant residues in the active site of the methyltransferase domain suggests a novel Mg{sup 2+}-dependent 2'-O-methylation mechanism.},

  doi          = {10.1038/nature08433},

  url          = {https://www.osti.gov/biblio/1005953},
  journal      = {Nature},
number       = 10, 2009,

  volume       = 461,

  place        = {United States},

  year         = {Mon Feb 22 00:00:00 EST 2010},

  month        = {Mon Feb 22 00:00:00 EST 2010}

}

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