lncRNAs in Stress Response
All living organisms sense and respond to harmful changes in their intracellular and extracellular environment through complex signaling pathways that lead to changes in gene expression and cellular function in order to maintain homeostasis. Long non-coding RNAs (lncRNAs), a large and heterogeneous group of functional RNAs, play important roles in cellular response to stressful conditions. lncRNAs constitute a significant fraction of the genes differentially expressed in response to diverse stressful stimuli and, once induced, contribute to the regulation of downstream cellular processes, including feedback regulation of key stress response proteins. While many lncRNAs seem to be induced in response to a specific stress, there is significant overlap between lncRNAs induced in response to different stressful stimuli. In addition to stress-induced RNAs, several constitutively expressed lncRNAs also exert a strong regulatory impact on the stress response. Although our understanding of the contribution of lncRNAs to the cellular stress response is still highly rudimentary, the existing data point to the presence of a complex network of lncRNAs, miRNAs, and proteins in regulation of the cellular response to stress.
KeywordsHeat Shock Response Hypoxic Response Bidirectional Promoter Genotoxic Agent Stress Response Pathway
Funding for this work was provided by CFAR grant number P30-AI036219 to S.V. and a postdoctoral scholarship from the National Board of Science and Technology of Mexico to A.V.H. The authors declare no conflict of interest.
- Erickson L, Highsmith jr E, Fei P, Zhang J (2015) Targeting the hypoxia pathway to treat pancreatic and cancer. Drug Des Dev Ther 2029. doi: 10.2147/DDDT.S80888
- Eymery A, Souchier C, Vourc’h C, Jolly C (2010) Heat shock factor 1 binds to and transcribes satellite II and III sequences at several pericentromeric regions in heat-shocked cells. Exp Cell Res 316:1845–1855. doi: 10.1016/j.yexcr.2010.02.002
- Kaidi A, Qualtrough D, Williams AC, Paraskeva C (2006) Direct transcriptional up-regulation of cyclooxygenase-2 by hypoxia-inducible factor (HIF)-1 promotes colorectal tumor cell survival and enhances HIF-1 transcriptional activity during hypoxia. Cancer Res 66:6683–6691. doi: 10.1158/0008-5472.CAN-06-0425 PubMedCrossRefGoogle Scholar
- Kino T, Hurt DE, Ichijo T, et al (2010) Noncoding RNA Gas5 Is a growth arrest- and starvation-associated repressor of the glucocorticoid receptor. Sci Signal 3:ra8–ra8. doi: 10.1126/scisignal.2000568
- Lakhotia SC, Mallik M, Singh AK, Ray M (2012) The large noncoding hsrω-n transcripts are essential for thermotolerance and remobilization of hnRNPs, HP1 and RNA polymerase II during recovery from heat shock in Drosophila. Chromosoma 121:49–70. doi: 10.1007/s00412-011-0341-x PubMedCrossRefGoogle Scholar
- Metz A, Soret J, Vourc’h C et al (2004) A key role for stress-induced satellite III transcripts in the relocalization of splicing factors into nuclear stress granules. J Cell Sci 117:4551–4558. doi: 10.1242/jcs.01329
- Ning Y, Yong F, Haibin Z et al (2015) LincRNA-p21 activates endoplasmic reticulum stress and inhibits hepatocellular carcinomaGoogle Scholar
- Nogalska A, Engel WK, Askanas V (2010) Increased BACE1 mRNA and noncoding BACE1-antisense transcript in sporadic inclusion-body myositis muscle fibers–possibly caused by endoplasmic reticulum stress. Neurosci Lett 474:140–143. doi: 10.1016/j.neulet.2010.03.023 PubMedPubMedCentralCrossRefGoogle Scholar
- Ramalingam M, Kim S-J (2012) Reactive oxygen/nitrogen species and their functional correlations in neurodegenerative diseases. J Neural Trans. doi: 10.1007/s00702-011-0758-7 (Vienna, Austria: 1996)
- Wunderlich M, Gross-Hardt R, Schöffl F (2014) Heat shock factor HSFB2a involved in gametophyte development of Arabidopsis thaliana and its expression is controlled by a heat-inducible long non-coding antisense RNA. Plant Mol Biol 85:541–550. doi: 10.1007/s11103-014-0202-0 PubMedPubMedCentralCrossRefGoogle Scholar