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Grc3 programs the essential endoribonuclease Las1 for specific RNA cleavage.

Publication ,  Journal Article
Pillon, MC; Sobhany, M; Borgnia, MJ; Williams, JG; Stanley, RE
Published in: Proc Natl Acad Sci U S A
July 11, 2017

Las1 is a recently discovered endoribonuclease that collaborates with Grc3-Rat1-Rai1 to process precursor ribosomal RNA (rRNA), yet its mechanism of action remains unknown. Disruption of the mammalian Las1 gene has been linked to congenital lethal motor neuron disease and X-linked intellectual disability disorders, thus highlighting the necessity to understand Las1 regulation and function. Here, we report that the essential Las1 endoribonuclease requires its binding partner, the polynucleotide kinase Grc3, for specific C2 cleavage. Our results establish that Grc3 drives Las1 endoribonuclease cleavage to its targeted C2 site both in vitro and in Saccharomyces cerevisiae. Moreover, we observed Las1-dependent activation of the Grc3 kinase activity exclusively toward single-stranded RNA. Together, Las1 and Grc3 assemble into a tetrameric complex that is required for competent rRNA processing. The tetrameric Grc3/Las1 cross talk draws unexpected parallels to endoribonucleases RNaseL and Ire1, and establishes Grc3/Las1 as a unique member of the RNaseL/Ire1 RNA splicing family. Together, our work provides mechanistic insight for the regulation of the Las1 endoribonuclease and identifies the tetrameric Grc3/Las1 complex as a unique example of a protein-guided programmable endoribonuclease.

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Published In

Proc Natl Acad Sci U S A

DOI

EISSN

1091-6490

Publication Date

July 11, 2017

Volume

114

Issue

28

Start / End Page

E5530 / E5538

Location

United States

Related Subject Headings

  • Two-Hybrid System Techniques
  • Saccharomyces cerevisiae Proteins
  • Saccharomyces cerevisiae
  • Ribosomes
  • Recombinant Proteins
  • RNA, Ribosomal
  • RNA Processing, Post-Transcriptional
  • RNA Precursors
  • Protein Multimerization
  • Protein Domains
 

Citation

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Pillon, M. C., Sobhany, M., Borgnia, M. J., Williams, J. G., & Stanley, R. E. (2017). Grc3 programs the essential endoribonuclease Las1 for specific RNA cleavage. Proc Natl Acad Sci U S A, 114(28), E5530–E5538. https://doi.org/10.1073/pnas.1703133114
Pillon, Monica C., Mack Sobhany, Mario J. Borgnia, Jason G. Williams, and Robin E. Stanley. “Grc3 programs the essential endoribonuclease Las1 for specific RNA cleavage.Proc Natl Acad Sci U S A 114, no. 28 (July 11, 2017): E5530–38. https://doi.org/10.1073/pnas.1703133114.
Pillon MC, Sobhany M, Borgnia MJ, Williams JG, Stanley RE. Grc3 programs the essential endoribonuclease Las1 for specific RNA cleavage. Proc Natl Acad Sci U S A. 2017 Jul 11;114(28):E5530–8.
Pillon, Monica C., et al. “Grc3 programs the essential endoribonuclease Las1 for specific RNA cleavage.Proc Natl Acad Sci U S A, vol. 114, no. 28, July 2017, pp. E5530–38. Pubmed, doi:10.1073/pnas.1703133114.
Pillon MC, Sobhany M, Borgnia MJ, Williams JG, Stanley RE. Grc3 programs the essential endoribonuclease Las1 for specific RNA cleavage. Proc Natl Acad Sci U S A. 2017 Jul 11;114(28):E5530–E5538.
Journal cover image

Published In

Proc Natl Acad Sci U S A

DOI

EISSN

1091-6490

Publication Date

July 11, 2017

Volume

114

Issue

28

Start / End Page

E5530 / E5538

Location

United States

Related Subject Headings

  • Two-Hybrid System Techniques
  • Saccharomyces cerevisiae Proteins
  • Saccharomyces cerevisiae
  • Ribosomes
  • Recombinant Proteins
  • RNA, Ribosomal
  • RNA Processing, Post-Transcriptional
  • RNA Precursors
  • Protein Multimerization
  • Protein Domains