Nucleolar Integrity Group | National Institute of Environmental Health Sciences

Nucleolar Integrity Group | National Institute of Environmental Health Sciences
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Molecular & Cellular Biology Laboratory
Robin E. Stanley, Ph.D.
Stadtman Investigator
Tel 984-287-3568
[email protected]
Research Summary
Robin Evans Stanley, Ph.D., leads the Nucleolar Integrity Group. The Nucleolar Integrity Group investigates molecular machines involved in critical RNA processing pathways through a multidisciplinary approach combining structural, molecular, and cellular biology. Currently the lab is focused on three major research areas including ribosome assembly, tRNA processing, and viral RNA processing.
This image was made with Biorender
Ribosome Assembly:
All cells required ribosomes for the translation of mRNA into proteins. Eukaryotic ribosome biogenesis is a complex process that involves the assembly of 79 ribosomal proteins with 4 ribosomal RNAs through the concerted effort of more than 200 non-ribosomal biogenesis factors within the nucleolus of the cell. Dysfunction of this pathway gives rise to a group of human diseases known as ribosomopathies and deregulation of the pathway had been linked with numerous types of human cancers. Ribosome biogenesis is one of the most energetically costly endeavors for a cell, at times using up to 80 percent of cellular energy resources. As a result, the process needs to be tightly regulated with cell cycle progress and environmental stimuli. Current work in the Stanley Lab is focused on determining how molecular machines involved in ribosome assembly, such as AAA-ATPases and endoribonucleases, are regulated.
Recent Publications:
Gordon J, Chapus FL, Viverette EG, Williams JG, Deterding LJ, Krahn JM, Borgnia MJ, Rodriguez J, Warren AJ, Stanley RE. Cryo-EM reveals the architecture of the PELP1-WDR18 molecular scaffold.
Nat Commun
. 2022;13(1):6783. Published 2022 Nov 9. doi:10.1038/s41467-022-34610-0 [
Abstract
Gordon J, Chapus FL, Viverette EG, Williams JG, Deterding LJ, Krahn JM, Borgnia MJ, Rodriguez J, Warren AJ, Stanley RE. Cryo-EM reveals the architecture of the PELP1-WDR18 molecular scaffold. Nat Commun. 2022;13(1):6783. Published 2022 Nov 9. doi:10.1038/s41467-022-34610-0
Kocaman S, Lo YH, Krahn JM, Sobhany M, Dandey VP, Petrovich ML, Etigunta SK, Williams JG, Deterding LJ, Borgnia MJ, Stanley RE. Communication network within the essential AAA-ATPase Rix7 drives ribosome assembly.
PNAS Nexus
. 2022;1(4):pgac118. Published 2022 Jul 21. doi:10.1093/pnasnexus/pgac118 [
Abstract
Kocaman S, Lo YH, Krahn JM, Sobhany M, Dandey VP, Petrovich ML, Etigunta SK, Williams JG, Deterding LJ, Borgnia MJ, Stanley RE. Communication network within the essential AAA-ATPase Rix7 drives ribosome assembly. PNAS Nexus. 2022;1(4):pgac118. Published 2022 Jul 21. doi:10.1093/pnasnexus/pgac118
Hayne CK, Lewis TA, Stanley RE. Recent insights into the structure, function, and regulation of the eukaryotic transfer RNA splicing endonuclease complex.
Wiley Interdiscip Rev RNA
. 2022;13(5):e1717. doi:10.1002/wrna.1717 [
Abstract
Hayne CK, Lewis TA, Stanley RE. Recent insights into the structure, function, and regulation of the eukaryotic transfer RNA splicing endonuclease complex. Wiley Interdiscip Rev RNA. 2022;13(5):e1717. doi:10.1002/wrna.1717
Frazier MN, Riccio AA, Wilson IM, Copeland WC, Stanley RE. Recent insights into the structure and function of coronavirus ribonucleases.
FEBS Open Bio
. 2022;12(9):1567-1583. doi:10.1002/2211-5463.13414 [
Abstract
Frazier MN, Riccio AA, Wilson IM, Copeland WC, Stanley RE. Recent insights into the structure and function of coronavirus ribonucleases. FEBS Open Bio. 2022;12(9):1567-1583. doi:10.1002/2211-5463.13414
Wilson IM, Frazier MN, Li JL, Randall TA, Stanley RE. Biochemical characterization of emerging SARS-CoV-2 nsp15 endoribonuclease variants.
J Mol Biol
. 2022;434(20):167796. doi:10.1016/j.jmb.2022.167796 [
Abstract
Wilson IM, Frazier MN, Li JL, Randall TA, Stanley RE. Biochemical characterization of emerging SARS-CoV-2 nsp15 endoribonuclease variants. J Mol Biol. 2022;434(20):167796. doi:10.1016/j.jmb.2022.167796
Frazier MN, Wilson IM, Krahn JM, Butay KJ, Dillard LB, Borgnia MJ, Stanley RE. Flipped over U: structural basis for dsRNA cleavage by the SARS-CoV-2 endoribonuclease.
Nucleic Acids Res
. 2022;50(14):8290-8301. doi:10.1093/nar/gkac589 [
Abstract
Frazier MN, Wilson IM, Krahn JM, Butay KJ, Dillard LB, Borgnia MJ, Stanley RE. Flipped over U: structural basis for dsRNA cleavage by the SARS-CoV-2 endoribonuclease. Nucleic Acids Res. 2022;50(14):8290-8301. doi:10.1093/nar/gkac589
Frazier MN, Pillon MC, Kocaman S, Gordon J, Stanley RE. Structural overview of macromolecular machines involved in ribosome biogenesis.
Curr Opin Struct Biol.
2020. 67:51-60. [
Abstract
Frazier MN, Pillon MC, Kocaman S, Gordon J, Stanley RE. Structural overview of macromolecular machines involved in ribosome biogenesis. Curr Opin Struct Biol. 2020. 67:51-60.
Pillon MC, Goslen KH, J Gordon, MJ Wells, Williams JG, Stanley RE. 2020. It takes two (Las1 HEPN endoribonuclease Domains) to cut RNA correctly.
J Biol Chem
; doi: 10.1074/jbc.RA119.011193 [Online 27 March 2020]. [
Abstract
Pillon MC, Goslen KH, J Gordon, MJ Wells, Williams JG, Stanley RE. 2020. It takes two (Las1 HEPN endoribonuclease Domains) to cut RNA correctly. J Biol Chem; doi: 10.1074/jbc.RA119.011193 [Online 27 March 2020].
Pillon MC, Hsu AL, Krahn JM, Williams JG, Goslen KH, Sobhany M, Borgnia MJ, Stanley RE. 2019. Cryo-EM reveals active site coordination within a multienzyme pre-rRNA processing complex.
Nat Struct Mol Bio
26(9):830-839. [
Abstract
Pillon MC, Hsu AL, Krahn JM, Williams JG, Goslen KH, Sobhany M, Borgnia MJ, Stanley RE. 2019. Cryo-EM reveals active site coordination within a multienzyme pre-rRNA processing complex. Nat Struct Mol Bio 26(9):830-839.
Gordon J, Pillon MC, Stanley RE. 2019. Nol9 Is a Spatial Regulator for the Human ITS2 Pre-rRNA Endonuclease-Kinase Complex.
Journal of Molecular Biology
431(19):3771-3786. [
Abstract
Gordon J, Pillon MC, Stanley RE. 2019. Nol9 Is a Spatial Regulator for the Human ITS2 Pre-rRNA Endonuclease-Kinase Complex. Journal of Molecular Biology 431(19):3771-3786.
Lo YH, Sobhany M, Hsu AL, Ford BL, Krahn JM, Borgnia MJ, Stanley RE. Cryo-EM Structure of the Essential Ribosome Assembly AAA-ATPase Rix7.
Nature Communications
2019 10(1):513. [
Abstract
Lo YH, Sobhany M, Hsu AL, Ford BL, Krahn JM, Borgnia MJ, Stanley RE. Cryo-EM Structure of the Essential Ribosome Assembly AAA-ATPase Rix7. Nature Communications 2019 10(1):513.
tRNA Processing:
tRNAs are decoders of the genome and play a critical role in protein translation. Similar to ribosome biogenesis, the transcription and processing of tRNAs is heavily regulated in response to nutrient availability and environmental stress. tRNAs undergo numerous processing and modification steps before they can participate in translation. A subset of tRNAs contain introns that must be removed by the tRNA Splicing Endonuclease (TSEN) complex to form the anticodon helix. Mutations in the TSEN complex are associated with a family of rare neurodevelopmental diseases known as pontocerebellar hypoplasia (PCH), however the underlying pathogenesis for this disease is unknown. Current work in the Stanley Lab is focused on defining how the TSEN complex recognizes and processes pre-tRNA substrates.
Recent Publications:
Hayne CK, Schmidt CA, Haque MI, Matera AG, Stanley RE. 2020. Reconstitution of the human tRNA splicing endonuclease complex: Insight into the regulation of pre-tRNA cleavage.
Nucleic Acids Res
; doi: 10.1093/nar/gkaa438 [Online 1 June 2020]. [
Abstract
Hayne CK, Schmidt CA, Haque MI, Matera AG, Stanley RE. 2020. Reconstitution of the human tRNA splicing endonuclease complex: Insight into the regulation of pre-tRNA cleavage. Nucleic Acids Res; doi: 10.1093/nar/gkaa438 [Online 1 June 2020].
Viral RNA Processing:
RNA viruses encode for many different RNA processing enzymes that support viral replication and/or evasion of the immune response. Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is a single stranded RNA virus and the causative agent of the current COVID-19 global health pandemic. To evade activation of dsRNA sensors coronaviruses employ a uridine-specific endoribonuclease, known as Nsp15, to process dsRNA intermediates. Nsp15 is well conserved across the coronavirus family, and EndoU like enzymes are also found in the larger nidovirus family, underscoring the significance of Nsp15 for ssRNA viruses. Current work in the Stanley Lab is focused on defining how Nsp15 recognizes and processes viral RNA.
Recent Publications:
Pillon MC, Frazier MN, Dillard LB, Williams JG, Kocaman S, Krahn JM, Perera L, Hayne CK, Gordon J, Stewart ZD, Sobhany M, Deterding LJ, Hsu AL, Dandey VP, Borgnia MJ, Stanley RE. 2021. Cryo-EM structures of the SARS-CoV-2 endoribonuclease Nsp15 reveal insight into nuclease specificity and dynamics.
Nat Commun
; doi: 10.1038/s41467-020-20608-z [Online 27 January 2021]. [
Abstract
Pillon MC, Frazier MN, Dillard LB, Williams JG, Kocaman S, Krahn JM, Perera L, Hayne CK, Gordon J, Stewart ZD, Sobhany M, Deterding LJ, Hsu AL, Dandey VP, Borgnia MJ, Stanley RE. 2021. Cryo-EM structures of the SARS-CoV-2 endoribonuclease Nsp15 reveal insight into nuclease specificity and dynamics. Nat Commun; doi: 10.1038/s41467-020-20608-z [Online 27 January 2021].
Frazier MN, Dillard LB, Krahn JM, Perera L, Williams JG, Wilson IM, Stewart ZD, Pillon MC, Deterding LJ, Borgnia MJ, Stanley RE. 2021. Characterization of SARS2 Nsp15 nuclease activity reveals it's mad about U.
Nucleic Acids Res
; doi: 10.1093/nar/gkab719 [Online 17 August 2021]. [
Abstract
Frazier MN, Dillard LB, Krahn JM, Perera L, Williams JG, Wilson IM, Stewart ZD, Pillon MC, Deterding LJ, Borgnia MJ, Stanley RE. 2021. Characterization of SARS2 Nsp15 nuclease activity reveals it's mad about U. Nucleic Acids Res; doi: 10.1093/nar/gkab719 [Online 17 August 2021].
Stanley, an Earl Stadtman Senior Investigator, earned her B.S. in chemistry and B.A. in mathematics from the University of North Carolina at Charlotte. She earned her Ph.D. in molecular biophysics and biochemistry at Yale University, where she worked under Nobel Laureate Thomas Steitz. Before joining NIEHS in 2014, she was a postdoctoral fellow with James H. Hurley at the National Institute of Diabetes, Digestive, and Kidney Diseases.
Related Links
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- Environmental Factor, December 2021
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- Environmental Factor, October 2021
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- Environmental Factor, November 2021
Robin Stanley awarded tenure
- Environmental Factor, May 2021
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Last Reviewed: April 14, 2026