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Natalia Shcherbik, Ph.D.

Assistant Professor

Science Center 145A


State Research Center of Virology and Biotechnology, Russia

Fels Institute for Cancer Research, Temple University School of Medicine, USA, 2003


Research Interests

Research in my laboratory is focused on the ribosome – a complex molecular machine that performs synthesis of polypeptides in living cells. Using the simple eukaryotic model organism Saccharomyces cerevisiae, we seek answers to the following questions:

How does stress affect ribosomes? 

Exposure to reactive oxygen species (ROS) can lead to oxidative stress in the cell. Aside from causing damage, ROS may also function as signal transducers and activate stress-defense mechanisms. In our studies, we address the question of whether ribosomes could be part of this signaling network. We made an interesting discovery that low-dose oxidants can promote endonucleolytic cleavage of the Expansion Segment 7 (ES7) within 25S ribosomal RNA (rRNA) in yeast (Shedlovskiy, 2017). This rRNA region is located on the surface of the eukaryotic 60S ribosomal subunit and plays a largely uncharacterized regulatory role. Using a combination of genetic and biochemical approaches, we found that a chemical rather than enzymatic mechanism of hydrolysis is responsible for the rRNA strand scission within ES7. Most likely, the rRNA is attacked by hydroxyl radicals produced locally via Fenton reaction by redox-active iron (Fe2+) bound to this region of the ribosome (Zinskie, 2018). The ES7-cleaved ribosomes are translationally competent and may help cells to adapt to the high-intensity oxidative stress (Shedlovskiy, 2017). These findings suggest that ES7 cleavage may confer additional properties on the ribosomes that are beneficial for stress resistance. How exactly this occurs and whether ES7-cleaved ribosomes behave differently during translation is a subject of our current research. We attack these questions from several directions, including mutational analysis and biochemical approaches that utilize a reconstituted in vitro translation system.

How does co-translational protein Quality Control (QC) operate in cells?

Co-translational protein QC is a critical part of protein homeostasis, as up to 15% of all newly generated polypeptides in eukaryotic cells fail to fold or assemble properly. Recent studies have shown that cells begin to eliminate faulty polypeptides as soon as during translation and that these contranslational QC systems are of extreme importance for proper protein homeostasis. Dysfunctional co-translational QC may cause accumulation of aberrant polypeptides that contribute to neurodegeneration and cancer. The most studied mechanism of co-translational QC relies on enzymatic complexes of the Ubiquitin-Proteasome System (UPS) and operates on peptidyl-tRNAs associated with 60S ribosomal subunits. Additional co-translational QC mechanisms appear to exist, but they received limited experimental attention. In our lab, we are developing approaches to better track endogenous substrates of co-translational QC (Shcherbik, 2016). In these studies, we focus on characterization of unconventional QC substrates modified with ubiquitin in the association with ribosomes and the mechanisms of their clearance.

What are the mechanisms of ribosome degradation?

The process of ribosome biogenesis is well studied, however, the mechanisms underlying ribosome degradation are still poorly defined. As of today, two major pathways of ribosome decay have been described, the Nonfunctional Ribosome Decay (NRD) that eliminates defective ribosomes, and ribophagy, a form of autophagy that removes ribosomes in bulk upon starvation. In our lab, we explore additional models of degradation of ribosomes that allow cells to recognize and remove old ribosomes and thus maintain a healthy ribosome pool, important for error-free translation and successful adaptation to a constantly changing environment. In our studies, we have found that the E3 ubiquitin ligase Rsp5 is required for the integrity of ribosomal RNA (rRNA) by ubiquitinating ribosomal proteins on functional ribosomes (Shcherbik 2011). We also demonstrated that suppression of TOR signaling induces a distinct cytoplasmic form of ribosome degradation in yeast (Pestov 2012). Both Rsp5-dependent and rapamycin-induced cytoplasmic turnover of ribosomes are mechanistically distinct from ribophagy or NRD and involve nucleases (Pestov 2012). We are currently interested in finding additional molecular factors and pathways that promote ribosome stability and mediate ribosome degradation in the cytoplasm.


(Updated September 2018)

  1. 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, 293(37): 14237-48, September 2018
  2. Shedlovskiy D, Shcherbik N, Pestov DG. One-step hot formamide extraction of RNA from Saccharomyces cerevisiae. RNA Biol, 14(12): 1722-6, December 2017.
  3. Shedlovskiy D, Zinskie JA, Gardner E, Pestov DG, Shcherbik NEndonucleolytic cleavage in the expansion segment 7 of 25S rRNA is an early marker of low-level oxidative stress in yeast. J Biol Chem, 292(45): 18469-85, November 2017.
  4. Shcherbik N, Chernova TA, Chernoff YO, Pestov DG. Distinct types of translation termination generate substrates for ribosome-associated quality control. Nucleic Acids Res, 44(14): 6840-52, August 2016.
  5. Wang M, Parshin AV, Shcherbik N, Pestov DG. Reduced expression of the mouse ribosomal protein Rpl17 alters the diversity of mature ribosomes by enhancing production of shortened 5.8S rRNARNA, 21(7): 1240-8, July 2015.
  6. Shcherbik NGolgi-mediated glycosylation determines residency of the T2 RNase Rny1p in Saccharomyces cerevisiaeTraffic, 14(12): 1209-27, December 2013.
  7. Pestov DG, Shcherbik NRapid cytoplasmic turnover of yeast ribosomes in response to rapamycin inhibition of TOR. Mol Cell Biol, 32(11): 2135-44, Jun 2012.
  8. Shcherbik N, Pestov DG. The ubiquitin ligase Rsp5 is required for ribosome stability in Saccharomyces cerevisiaeRNA, 17(8): 1422-8, Aug 2011.
  9. Shcherbik N, Pestov DG. Ubiquitin and ubiquitin-like proteins in the nucleolus: multitasking tools for a ribosome factoryGenes Cancer, 1(7): 681-9,Jul 2010.
  10. Shcherbik N, Wang M, Lapik YR, Srivastava L, Pestov DG. Polyadenylation and degradation of incomplete RNA polymerase I transcripts in mammalian cells. EMBO Rep, 11(2): 106-11, Feb 2010.
  11. Bhattacharya S, Shcherbik N, Vasilescu J, Smith JC, Figeys D, Haines DS. Identification of lysines within membrane-anchored Mga2p120 that are targets of Rsp5p ubiquitination and mediate mobilization of tethered Mga2p90J Mol Biol, 385(3): 718-25, Jan 2009.
  12. Shcherbik N, Haines DS.  Cdc48pNpl4p/Ufd1p binds and segregates heterodimeric membrane anchored/tethered complexes via a polyubiquitin signal present on the anchors.  Molecular Cell, 25(3): 385-97, Feb 2007.
  13. Shcherbik N, Kee Y, Lyon N, Huibregtse JM, Haines DS.  A single PXY motif located within the carboxy-terminus of Spt23p and Mga2p mediates a physical and functional interaction with ubiquitin ligase Rsp5p.  J Biol Chem, 279(51): 53892-8, Dec 2004.
  14. Shcherbik N, Haines DS. Ub on the moveJ Cell Biochem, 93(1): 11-9, Sep 2004.
  15. Shcherbik N, Zoladek T, Nickels JT, Haines DS.  Rsp5p is required for ER-bound Mga2p120 poly-ubiquitination and release of the processed/tethered transactivator Mga2p90.  Curr Biol, 13(14): 1227-1233, Jul 2003.
  16. Gajewska B, Shcherbik N, Oficjalska D, Haines DS, Zoladek T.  Functional analysis of the human orthologue of the RSP5-encoded ubiquitin protein ligase,  hNEDD4, in yeast.  Curr Genet, 43(1): 1-10, Apr 2003.
  17. Shcherbik N, Kumar S, Haines DS. Substrate proteolysis is inhibited by dominant-negative Nedd4 and Rsp5 mutants harboring alterations in WW domain 1 J Cell Sci, 115(Pt5): 1041-8, Mar 2002.
  18. Darbinian N, Gallia GL, Kundu M, Shcherbik N, Tretiakova A, Giordano A, Khalili K. Association of Pur alpha and E2F-1 suppresses transcriptional activity of E2F-1Oncogene, 18(46): 6398-402, Nov 1999.
  19. Tretiakova A, Gallia GL, Shcherbik N, Jameson B, Johnson EM, Amini S, Khalili K. Association of Pur alpha with RNAs homologous to 7 SL determines its binding ability to the myelin basic protein promoter DNA sequenceJ Biol Chem, 273(35): 22241-7, Aug 1998.
  20. Safronov IV, Shcherbik NV, Khodyreva SN, Vlasov VA, Dobrikov MI, Shishkin GV, Lavrik OI. New photoreactive N(4)-substituted dCTP analogues: synthesis, photochemical characteristics, and substrate properties in HIV-1 reverse transcriptase catalyzed DNA synthesis. Bioorg Khim, 23(7): 576-85, Jul 1997.
  21. Shcherbik NV, Khodyreva SN, Vlasov VA, Dobrikov MI, Dymshits GM, Lavrik OI. Photoaffinity modification of human immunodeficiency virus reverse transcriptase with an analog of deoxyuridine-5'-triphosphate, containing an arylazide groupMol Biol (Mosk), 31(2): 344-52, Mar 1997.