The structure of the box C/D enzyme reveals regulation of RNA methylation

Audrone Lapinaite; Bernd Simon; Lars Skjaerven; Magdalena Rakwalska-Bange; Frank Gabel; Teresa Carlomagno

doi:10.1038/nature12581

The structure of the box C/D enzyme reveals regulation of RNA methylation

Audrone Lapinaite, Bernd Simon, Lars Skjaerven, Magdalena Rakwalska-Bange, Frank Gabel, Teresa Carlomagno

Biosciences

Research output: Contribution to journal › Article › peer-review

Abstract

Post-transcriptional modifications are essential to the cell life cycle, as they affect both pre-ribosomal RNA processing and ribosome assembly. The box C/D ribonucleoprotein enzyme that methylates ribosomal RNA at the 2'-O-ribose uses a multitude of guide RNAs as templates for the recognition of rRNA target sites. Two methylation guide sequences are combined on each guide RNA, the significance of which has remained unclear. Here we use a powerful combination of NMR spectroscopy and small-angle neutron scattering to solve the structure of the 390 kDa archaeal RNP enzyme bound to substrate RNA. We show that the two methylation guide sequences are located in different environments in the complex and that the methylation of physiological substrates targeted by the same guide RNA occurs sequentially. This structure provides a means for differential control of methylation levels at the two sites and at the same time offers an unexpected regulatory mechanism for rRNA folding.

Original language	English
Pages (from-to)	519-23
Number of pages	5
Journal	Nature
Volume	502
Issue number	7472
DOIs	https://doi.org/10.1038/nature12581
Publication status	Published - 24 Oct 2013

Keywords

Apoproteins/chemistry
Archaeal Proteins/chemistry
Biocatalysis
Chromosomal Proteins, Non-Histone/metabolism
Methylation
Models, Molecular
Multiprotein Complexes/chemistry
Nucleic Acid Conformation
Pyrococcus furiosus/enzymology
RNA Folding
RNA Processing, Post-Transcriptional
RNA, Archaeal/chemistry
RNA, Guide, Kinetoplastida/chemistry
RNA, Ribosomal/chemistry
Ribonucleoproteins, Small Nucleolar/chemistry

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title = "The structure of the box C/D enzyme reveals regulation of RNA methylation",

abstract = "Post-transcriptional modifications are essential to the cell life cycle, as they affect both pre-ribosomal RNA processing and ribosome assembly. The box C/D ribonucleoprotein enzyme that methylates ribosomal RNA at the 2'-O-ribose uses a multitude of guide RNAs as templates for the recognition of rRNA target sites. Two methylation guide sequences are combined on each guide RNA, the significance of which has remained unclear. Here we use a powerful combination of NMR spectroscopy and small-angle neutron scattering to solve the structure of the 390 kDa archaeal RNP enzyme bound to substrate RNA. We show that the two methylation guide sequences are located in different environments in the complex and that the methylation of physiological substrates targeted by the same guide RNA occurs sequentially. This structure provides a means for differential control of methylation levels at the two sites and at the same time offers an unexpected regulatory mechanism for rRNA folding.",

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author = "Audrone Lapinaite and Bernd Simon and Lars Skjaerven and Magdalena Rakwalska-Bange and Frank Gabel and Teresa Carlomagno",

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doi = "10.1038/nature12581",

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T1 - The structure of the box C/D enzyme reveals regulation of RNA methylation

AU - Lapinaite, Audrone

AU - Simon, Bernd

AU - Skjaerven, Lars

AU - Rakwalska-Bange, Magdalena

AU - Gabel, Frank

AU - Carlomagno, Teresa

PY - 2013/10/24

Y1 - 2013/10/24

N2 - Post-transcriptional modifications are essential to the cell life cycle, as they affect both pre-ribosomal RNA processing and ribosome assembly. The box C/D ribonucleoprotein enzyme that methylates ribosomal RNA at the 2'-O-ribose uses a multitude of guide RNAs as templates for the recognition of rRNA target sites. Two methylation guide sequences are combined on each guide RNA, the significance of which has remained unclear. Here we use a powerful combination of NMR spectroscopy and small-angle neutron scattering to solve the structure of the 390 kDa archaeal RNP enzyme bound to substrate RNA. We show that the two methylation guide sequences are located in different environments in the complex and that the methylation of physiological substrates targeted by the same guide RNA occurs sequentially. This structure provides a means for differential control of methylation levels at the two sites and at the same time offers an unexpected regulatory mechanism for rRNA folding.

AB - Post-transcriptional modifications are essential to the cell life cycle, as they affect both pre-ribosomal RNA processing and ribosome assembly. The box C/D ribonucleoprotein enzyme that methylates ribosomal RNA at the 2'-O-ribose uses a multitude of guide RNAs as templates for the recognition of rRNA target sites. Two methylation guide sequences are combined on each guide RNA, the significance of which has remained unclear. Here we use a powerful combination of NMR spectroscopy and small-angle neutron scattering to solve the structure of the 390 kDa archaeal RNP enzyme bound to substrate RNA. We show that the two methylation guide sequences are located in different environments in the complex and that the methylation of physiological substrates targeted by the same guide RNA occurs sequentially. This structure provides a means for differential control of methylation levels at the two sites and at the same time offers an unexpected regulatory mechanism for rRNA folding.

KW - Apoproteins/chemistry

KW - Archaeal Proteins/chemistry

KW - Biocatalysis

KW - Chromosomal Proteins, Non-Histone/metabolism

KW - Methylation

KW - Models, Molecular

KW - Multiprotein Complexes/chemistry

KW - Nucleic Acid Conformation

KW - Pyrococcus furiosus/enzymology

KW - RNA Folding

KW - RNA Processing, Post-Transcriptional

KW - RNA, Archaeal/chemistry

KW - RNA, Guide, Kinetoplastida/chemistry

KW - RNA, Ribosomal/chemistry

KW - Ribonucleoproteins, Small Nucleolar/chemistry

U2 - 10.1038/nature12581

DO - 10.1038/nature12581

M3 - Article

C2 - 24121435

SN - 0028-0836

VL - 502

SP - 519

EP - 523

JO - Nature

JF - Nature

IS - 7472

ER -

The structure of the box C/D enzyme reveals regulation of RNA methylation

Abstract

Keywords

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