Adverse stimuli, such as oxidative stress, thermal shock, viral infection, amongst others, consistently act upon cells to which they must respond to promote survival. Despite the variety of stresses, cells react similarly by conserving and redirecting energetic reserves from anabolic processes towards pro-survival processes. Precise modulation of a stress response is critical to organismal homeostasis. Failure to mount an effective response will result in cell death while a hyperactive response can lead to unrestrained proliferation or inflammation. Such situations are typically seen in neurodegenerative diseases and cancer, respectively.
The long-term goal of my laboratory is to understand how cells reprogram gene expression in response to stress, while specifically focusing on post-transcriptional regulation. Currently, there are two aspects to this response that my lab is investigating:
- Control of ribosomal RNA (rRNA) processing: Ribosome biogenesis is a major energetic task of growing cells; thus, this is a significant point of regulation during stress. Mature ribosomes contain 80 proteins and four non-coding RNAs. We aim to understand how maturation of rRNAs, which constitute the majority of all cellular RNA, is regulated under different conditions.
- Regulation of mRNA translation during stress: The activation of the integrated stress response (ISR) directly targets the translational machinery resulting in the rapid inhibition of protein synthesis. We aim to understand the mechanisms by which this occurs and how some mRNAs escape ISR-dependent regulation.
Sandeep Ojha – Postdoctoral Associate
Sulochan Malla – Postdoctoral Associate
positions available—contact Dr. Lyons
Aulas A, Lyons SM, Fay MM, Ivanov P, Anderson P. (2018) Nitric oxide triggers the assembly of “type II” stress granules linked to decreased cell viability. Cell Death and Disease, 9(11):1129. PMID: 30425239
Lyons SM, Fay MM, Ivanov P. (2018) The role of RNA modifications in tRNA cleavage. FEBS Letters. 592: 2828 – 2844. PMID: 30058219.
Lyons SM, Gudanis D, Gdaniec Z, Ivanov P. (2017) Identification of functional tetramolecular RNA G-quadruplexes derived from transfer RNAs. Nature Communications. 8(1):2020. PMID: 29066746
Fay MM, Lyons SM, Ivanov P. (2017) RNA G-quadruplexes in biology: Principles and molecular mechanisms. Journal of Molecular Biology. 429(14): 2127 – 2147. PMID: 28554731
Aulas A, Fay MM, Lyons SM, Achorn, CA, Kedersha, N, Anderson P, Ivanov P. (2017) Stress specific differences in assembly and composition of stress granules and related foci. Journal of Cell Science. 130(5) 927- 937. PMID: 28096475
Lyons SM, Fay MM, Akiyama Y, Anderson PJ, Ivanov P. (2017) RNA biology of angiogenin: Current state and perspectives. RNA Biology. 14(2): 171 – 178. PMID: 28010172
Lyons SM, Cunningham CH, Welch JD, Groh B, Guo AY, Wei B, Whitfield ML, Xiong Y, Marzluff WF. (2016) A subset of replication dependent histone mRNAs are expressed as polyadenylated RNAs in terminally differentiated tissues. Nucleic Acids Research. 44(19), 9190-9205. PMID: 27402160
Lyons SM, Anderson P (2016) RNA-seeded functional amyloids balance growth and survival. Developmental Cell. 39(2): 131-132. PMID: 27780035
Lyons SM, Achorn C, Kedersha NL, Anderson PJ, Ivanov P. (2016) YB-1 regulates tiRNA-induced stress granule formation but not translational repression. Nucleic Acids Research. 44(14): 6949 – 6960. PMID: 27174937
Mineo M, Rickles F, Rooj AK, Lyons SM, Ivanov P, Ansari KI, Nakano I, Chiocca EA, Godlewski, Bronisz A. (2016) The long non-coding RNA HIF1A-AS2 facilitates the maintenance of mesenchymal glioblastoma stem-like cells in hypoxic niches. Cell Reports 15(11), 2500 – 2509. PMID: 27264189
Kedersha N, Panas MD, Achorn CA, Lyons SM, Tisdale S, Hickman T, Thomas M, Lieberman J, McInerney GM, Ivanov P, Anderson P (2016) G3BP-Caprin1-USP10 complexes mediate stress granule condensation and associate with 40S subunits. Journal of Cell Biology 212(7): 845 – 860. PMID: 27022092
Johnson ME, Grassetti, AV, Taroni JN, Lyons SM, Schweppe D, Gordon JK, Spiera RF, Lafyatis R, Anderson PJ, Gerber SA, Whitfield ML (2016). Stress granules and RNA processing bodies are novel autoantibody targets in systemic sclerosis. Arthritis Research and Therapy 18(1): 27. PMID: 26801089
Brooks L, Lyons SM, Mahoney JM, Liu Z, Marzluff WF, Whitfield ML. (2015) A multiprotein occupancy map of the mRNP on the 3’ end of histone mRNAs. RNA 21(11) 1943 – 1965. PMID: 26377992
Terzo EA, Lyons SM, Poulton JS, Temple BRS Marzluff WF, Duronio RJ. Distinct self-interaction domains promote Multiple Sex Combs accumulation in and formation of the Drosophila Histone Locus Body. (2015). Molecular Biology of the Cell 26(8): 1559 – 1574. PMID: 25694448
Lyons SM, Guo AY, Ricciardi AS, Kambach KS, Marzluff WF. (2014) The C-terminal extension of Lsm4 interacts directly with the 3’ end of the histone mRNP and is required for efficient histone mRNA. RNA 20(1) 88 – 102. PMID: 24255165
Su W, Slepenkov SV, Slevin MK, Lyons SM, Ziemniak M, Kowalska J, Darzynkiewicz E, Jemielity J, Marzluff WF, Rhoads RE. (2013) 3’-Oligouridylation is an obligatory step for degradation of an mRNA containing the histone 3’-Stem-Loop. RNA. 19(1): 1-16. PMID: 23188809
Martin L, Meier M, Lyons SM, Sit RV, Marzluff WF, Quake SR, Chang HY. (2012) Systematic reconstruction of RNA functional motifs with high-throughput microfluidics. Nature Methods. 9(12): 1192 -1194. PMID: 23142872
Yang T, Lyons S, Aguilar C, Cuhel R, Teske A. (2011). Microbial communities and chemosynthesis in Yellowstone Lake sublacustrine hydrothermal vent waters. Frontiers in Microbiology. 2:130. PMID: 21716640