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Las1 interacts with Grc3 polynucleotide kinase and is required for ribosome synthesis in Saccharomyces cerevisiae.
Nucleic Acids Res. 2013 Jan; 41(2):1135-50.NA

Abstract

Ribosome biogenesis is a multi-step process that couples cell growth with cell proliferation. Although several large-scale analysis of pre-ribosomal particles have identified numerous trans-acting factors involved in this process, many proteins involved in pre-rRNA processing and ribosomal subunit maturation have yet to be identified. Las1 was originally identified in Saccharomyces cerevisiae as a protein involved in cell morphogenesis. We previously demonstrated that the human homolog, Las1L, is required for efficient ITS2 rRNA processing and synthesis of the 60S ribosomal subunit. Here, we report that the functions of Las1 in ribosome biogenesis are also conserved in S. cerevisiae. Depletion of Las1 led to the accumulation of both the 27S and 7S rRNA intermediates and impaired the synthesis of the 60S subunit. We show that Las1 co-precipitates mainly with the 27S rRNA and associates with an Nsa1 and Rix1-containing pre-60S particle. We further identify Grc3 as a major Las1-interacting protein. We demonstrate that the kinase activity of Grc3 is required for efficient pre-rRNA processing and that depletion of Grc3 leads to rRNA processing defects similar to the ones observed in Las1-depleted cells. We propose that Las1 and Grc3 function together in a conserved mechanism to modulate rRNA processing and eukaryotic ribosome biogenesis.

Authors+Show Affiliations

Department of Integrative Biology and Pharmacology, Graduate School of Biomedical Sciences, The University of Texas Health Science Center, Houston, TX 77030, USA.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

23175604

Citation

Castle, Christopher D., et al. "Las1 Interacts With Grc3 Polynucleotide Kinase and Is Required for Ribosome Synthesis in Saccharomyces Cerevisiae." Nucleic Acids Research, vol. 41, no. 2, 2013, pp. 1135-50.
Castle CD, Sardana R, Dandekar V, et al. Las1 interacts with Grc3 polynucleotide kinase and is required for ribosome synthesis in Saccharomyces cerevisiae. Nucleic Acids Res. 2013;41(2):1135-50.
Castle, C. D., Sardana, R., Dandekar, V., Borgianini, V., Johnson, A. W., & Denicourt, C. (2013). Las1 interacts with Grc3 polynucleotide kinase and is required for ribosome synthesis in Saccharomyces cerevisiae. Nucleic Acids Research, 41(2), 1135-50. https://doi.org/10.1093/nar/gks1086
Castle CD, et al. Las1 Interacts With Grc3 Polynucleotide Kinase and Is Required for Ribosome Synthesis in Saccharomyces Cerevisiae. Nucleic Acids Res. 2013;41(2):1135-50. PubMed PMID: 23175604.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Las1 interacts with Grc3 polynucleotide kinase and is required for ribosome synthesis in Saccharomyces cerevisiae. AU - Castle,Christopher D, AU - Sardana,Richa, AU - Dandekar,Varada, AU - Borgianini,Victoria, AU - Johnson,Arlen W, AU - Denicourt,Catherine, Y1 - 2012/11/21/ PY - 2012/11/24/entrez PY - 2012/11/24/pubmed PY - 2013/4/5/medline SP - 1135 EP - 50 JF - Nucleic acids research JO - Nucleic Acids Res. VL - 41 IS - 2 N2 - Ribosome biogenesis is a multi-step process that couples cell growth with cell proliferation. Although several large-scale analysis of pre-ribosomal particles have identified numerous trans-acting factors involved in this process, many proteins involved in pre-rRNA processing and ribosomal subunit maturation have yet to be identified. Las1 was originally identified in Saccharomyces cerevisiae as a protein involved in cell morphogenesis. We previously demonstrated that the human homolog, Las1L, is required for efficient ITS2 rRNA processing and synthesis of the 60S ribosomal subunit. Here, we report that the functions of Las1 in ribosome biogenesis are also conserved in S. cerevisiae. Depletion of Las1 led to the accumulation of both the 27S and 7S rRNA intermediates and impaired the synthesis of the 60S subunit. We show that Las1 co-precipitates mainly with the 27S rRNA and associates with an Nsa1 and Rix1-containing pre-60S particle. We further identify Grc3 as a major Las1-interacting protein. We demonstrate that the kinase activity of Grc3 is required for efficient pre-rRNA processing and that depletion of Grc3 leads to rRNA processing defects similar to the ones observed in Las1-depleted cells. We propose that Las1 and Grc3 function together in a conserved mechanism to modulate rRNA processing and eukaryotic ribosome biogenesis. SN - 1362-4962 UR - https://www.unboundmedicine.com/medline/citation/23175604/Las1_interacts_with_Grc3_polynucleotide_kinase_and_is_required_for_ribosome_synthesis_in_Saccharomyces_cerevisiae_ L2 - https://academic.oup.com/nar/article-lookup/doi/10.1093/nar/gks1086 DB - PRIME DP - Unbound Medicine ER -