SHCHERBIK/PESTOV LAB
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Our research.

Research in our laboratories focuses on ribosome biology and co-translational protein quality control. Every protein in cells is made by ribosomes, complex molecular machines assembled from multiple RNA and protein components. One question we address in our studies is how cells mitigate defects in ribosome biogenesis, which are known to be detrimental for protein synthesis and could compromise a variety of cellular functions. The second line of our labs’ research is to understand what happens to ribosomes that become damaged during their lifecycle in the cell. Our studies have shown that environmental factors such as oxidative stress, exposure to toxic metals, and metabolic diseases may induce molecular damage in ribosomal components, leading to ribosome malfunction. We are using yeast and mammalian systems to investigate the mechanisms by which the cells minimize impact of the malfunctioning ribosomes on cellular proteostasis. Through this research, we hope to obtain new insights into pathological changes of the proteome associated with environmental stress, aging, and neurodegenerative diseases.
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Original Research

  • Trainor BM, Komar AA, Pestov DG, Shcherbik N. Cell-free Translation: Preparation and Validation of Translation-competent Extracts from Saccharomyces cerevisiae. BioProtocols. 2021. Sep 20;11(18):e4093.doi: 10.21769/BioProtoc.4093.
  • Nieto B, Gaspar SG, Sapio RT, Clavaín L, Bustelo XR, Pestov DG, Dosil M. Efficient fractionation and analysis of ribosome assembly intermediates in human cells. 2021. Sep 17;1-16.doi: 10.1080/15476286.2021.1965754.
  • Brandon M. Trainor, Dimitri G. Pestov and Natalia Shcherbik. Development, validation, and application of the ribosome separation and reconstitution system for protein translation in vitro. RNA. 2021 Aug 27; rna.078852.121. doi: 10.1261/rna.078852.121.
  • Sapio RT, Burns CJ, Pestov DG. Effects of Hydrogen Peroxide Stress on the Nucleolar Redox Environment and Pre-rRNA Maturation. Front Mol Biosci. 2021 Apr 26;8:678488. doi: 10.3389/fmolb.2021.678488. eCollection 2021.​​​
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  • ​Wang X, Zhang H, Sapio R, Yang J, Wong J, Zhang X, Guo JY, Pine S, Van Remmen H, Li H, White E, Liu C, Kiledjian M, Pestov DG, Steven Zheng XF. SOD1 regulates ribosome biogenesis in KRAS mutant non-small cell lung cancer. Nat Commun. 2021 Apr 15;12(1):2259. doi: 10.1038/s41467-021-22480-x.
  • Wang Y, Fang S, Chen G, Ganti R, Chernova TA, Zhou L, Duong D, Kiyokawa H, Li M, Zhao B, Shcherbik N, Chernoff YO, Yin J. Regulation of the endocytosis and prion-chaperoning machineries by yeast E3 ubiquitin ligase Rsp5 as revealed by orthogonal ubiquitin transfer. Cell Chem Biol. 2021 Feb 23:S2451-9456(21)00057-X. doi: 10.1016/j.chembiol.2021.02.005. 
  • Trainor BM, Ghosh A, Pestov DG, Hellen CUT, Shcherbik N. A translation enhancer element from black beetle virus engages yeast eIF4G1 to drive cap-independent translation initiation. Scientific Reports. 2021. Jan 28; 11(1): 2461. doi: 10.1038/s41598-021-82025-6.
  • Caiyong Ye, Bochao Liu, Huimei Lu, Jingmei Liu, Arnold B Rabson, Estela Jacinto, Dimitri G Pestov, Zhiyuan Shen.  BCCIP is required for nucleolar recruitment of eIF6 and 12S pre-rRNA production during 60S ribosome biogenesis. Nucleic Acids Res. 2020 Dec 16; 48(22): 12817–12832. Published online 2020 Nov 27. doi: 10.1093/nar/gkaa1114
  • Daniel G J Smethurst, Nikolay Kovalev, Erica R McKenzie, Dimitri G Pestov, Natalia Shcherbik. Iron-mediated degradation of ribosomes under oxidative stress is attenuated by manganese. J Biol Chem. 2020. Dec 11; 295(50): 17200-17214.
  • ​Ghosh A, Shcherbik N. Cooperativity between the Ribosome-Associated Chaperone Ssb/RAC and the Ubiquitin Ligase Ltn1 in Ubiquitination of Nascent Polypeptides. IJMS. 2020. Sept 17; 21(18): 6815.​​
  • Chernova TA, Yang Z, Karpova TS, Shanks JR, Shcherbik N, Wilkinson KD, Chernoff YO. Aggregation and Prion-Inducing Properties of the G-Protein Gamma Subunit Ste18 are Regulated by Membrane Association. IJMS. 2020. July 16; 21(14): 5038.
  • Ghosh A, Williams LD, Pestov DG and Shcherbik N. Proteotoxic stress promotes entrapment of ribosomes and misfolded proteins in a shared cytosolic compartment. Nucleic Acids Res. 2020. Apr 17; 48(7): 3888-3905.
  • Nieto B, Gaspar SG, Moriggi G, Pestov DG, Bustelo XR, Dosil M. Identification of distinct maturation steps involved in human 40S ribosomal subunit biosynthesis. Nat Commun. 2020. Jan 9;11(1):156. 
  • Zinskie JA, Ghosh A, Trainor BM, Shedlovskiy D, Pestov DG, Shcherbik N. Iron-dependent cleavage of ribosomal RNA during oxidative stress in the yeast Saccharomyces cerevisiae. J Biol Chem. 2018. Sep 14;293(37):14237-14248.
  • Daniel Shedlovskiy, Jessica A. Zinskie, Ethan Gardner, Dimitri G. Pestov and Natalia Shcherbik. Endonucleolytic cleavage in the expansion segment 7 of 25S rRNA is an early marker of low-level oxidative stress in yeast. J Biol Chem. 2017. Nov 10;292(45):18469-18485. 
  • Sapio RT, Nezdyur AN, Krevetski M, Anikin L, Manna VJ, Minkovsky N, Pestov DG. Inhibition of post-transcriptional steps in ribosome biogenesis confers cytoprotection against chemotherapeutic agents in a p53-dependent manner. Sci Rep. 2017. Aug 22;7(1):9041. 
  • Shedlovski D, Shcherbik N, Pestov D. One-step hot formamide extraction of RNA from Saccharomyces cerevisiae. RNA Biology. 2017. Jul 10:1-5.
  • Shcherbik N, Chernova TA, Chernoff JO, Pestov DG. Distinct types of translation termination generate substrates for ribosome-associated quality control. Nucleic Acid Research. 2016. 44(14): 6840-52.
  • Wang M, Pestov DG. Quantitative Northern Blot Analysis of Mammalian rRNA Processing. Methods Mol Biol. 2016. 1455:147-57.
  • Wang M, Parshin A, Shcherbik N and Pestov D.G. Reduced expression of the mouse ribosomal protein Rpl17 alters the diversity of mature ribosomes by enhancing production of shortened 5.8S rRNA. RNA. 2015. 21(7):1240-8.
  • Wang M, Anikin L, Pestov DG. Two orthogonal cleavages separate subunit RNAs in mouse ribosome biogenesis. Nucleic Acids Res. 2014. 42(17):11180-91.
  • Mansour FH, Pestov DG. Separation of long RNA by agarose-formaldehyde gel electrophoresis. Anal Biochem. 2013. Oct 1;441(1):18-20.
  • Shcherbik N. Golgi-mediated glycosylation determines residency of the T2 RNase Rny1p in Saccharomyces cerevisiae. Traffic. 2013. 14(12), 1209-27.
  • Pestov DG, Shcherbik N. Rapid cytoplasmic turnover of yeast ribosomes in response to rapamycin inhibition of TOR. Mol Cell Biol. 2012. 32(11): 2135-44.
  • Wang M, Pestov DG. 5'-end surveillance by Xrn2 acts as a shared mechanism for mammalian pre-rRNA maturation and decay. Nucleic Acids Res. 2011. Mar;39(5):1811-22.
  • Shcherbik N, Pestov DG. The ubiquitin ligase Rsp5 is required for ribosome stability in Saccharomyces cerevisiae. RNA. 2011. 17: 1422-1428.
  • Srivastava L, Lapik YR, Wang M, Pestov DG. Mammalian DEAD box protein Ddx51 acts in 3' end maturation of 28S rRNA by promoting the release of U8 snoRNA. Mol Cell Biol. 2010. Jun; 30(12):2947-56.  
  • Shcherbik N, Wang M, Lapik YR, Srivastava L, Pestov DG. Polyadenylation and degradation of incomplete RNA polymerase I transcripts in mammalian cells. EMBO Rep. 2010. 11: 106-111.

Reviews

  • Smethurst DGJ, Shcherbik N. Interchangeable utilization of metals: New perspectives on the impacts of metal ions employed in ancient and extant biomolecules. J. Biol. Chem. 2021. Oct 31: 297(6):101374.
  • Santerre M, Arjona SP, Allen CN, Shcherbik N, Sawaya BE. Why do SARS-CoV-2 NSPs rush to the ER? J Neurology. 2020, Sept 1: 1-10.
  • Ghosh A and Shcherbik N. Effects of Oxidative Stress on Protein Translation: Implications for Cardiovascular Diseases. IJMS. 202 Apr 11; 21(8).
  • Shcherbik N and Pestov DG. The Impact of Oxidative Stress on Ribosomes: From Injury to Regulation. Cells. 2019 Nov 2; 8(11).
  • Shcherbik, N; and Pestov, D.G. Ubiquitin and ubiquitin-like proteins in the nucleolus: multitasking tools for a ribosome factory. Genes Cancer 1: 681-689, 2010. 

Our research is supported by

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