Search for microRNAs expressed by intracellular bacterial pathogens in infected mammalian cells.
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MicroRNAs are expressed by all multicellular organisms and play a critical role as post-transcriptional regulators of gene expression. Moreover, different microRNA species are known to influence the progression of a range of different diseases, including cancer and microbial infections. A number of different human viruses also encode microRNAs that can attenuate cellular innate immune responses and promote viral replication, and a fungal pathogen that infects plants has recently been shown to express microRNAs in infected cells that repress host cell immune responses and promote fungal pathogenesis. Here, we have used deep sequencing of total expressed small RNAs, as well as small RNAs associated with the cellular RNA-induced silencing complex RISC, to search for microRNAs that are potentially expressed by intracellular bacterial pathogens and translocated into infected animal cells. In the case of Legionella and Chlamydia and the two mycobacterial species M. smegmatis and M. tuberculosis, we failed to detect any bacterial small RNAs that had the characteristics expected for authentic microRNAs, although large numbers of small RNAs of bacterial origin could be recovered. However, a third mycobacterial species, M. marinum, did express an ∼ 23-nt small RNA that was bound by RISC and derived from an RNA stem-loop with the characteristics expected for a pre-microRNA. While intracellular expression of this candidate bacterial microRNA was too low to effectively repress target mRNA species in infected cultured cells in vitro, artificial overexpression of this potential bacterial pre-microRNA did result in the efficient repression of a target mRNA. This bacterial small RNA therefore represents the first candidate microRNA of bacterial origin.
Gene Expression Regulation
High-Throughput Nucleotide Sequencing
Published Version (Please cite this version)10.1371/journal.pone.0106434
Publication InfoCoers, Jorn; Cullen, BR; Finethy, Ryan; Furuse, Y; Lee, S; Saka, HA; ... Xet-Mull, AM (2014). Search for microRNAs expressed by intracellular bacterial pathogens in infected mammalian cells. PLoS One, 9(9). pp. e106434. 10.1371/journal.pone.0106434. Retrieved from http://hdl.handle.net/10161/11186.
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Associate Professor in Molecular Genetics and Microbiology
James B. Duke Professor of Molecular Genetics and Microbiology
My laboratory has for sometime been interested in understanding the molecular biology of the replication cycle of the pathogenic retrovirus HIV-1. Because HIV-1 gene expression is primarily regulated by specific RNA:protein interactions, my laboratory has also become interested in the more general area of RNA sequence mediated gene regulation, including nuclear mRNA export and the phenomenon of RNA interference. In the past, my laboratory has worked extensively on Tat, the trans
Professor of Molecular Genetics and Microbiology
My laboratory is interested in how microbes influence human health, both in the context of host-pathogen and host-commensal interactions. For many pathogens, and certainly for most commensal microbes, the molecular basis of how host and microbial factors contribute to a beneficial outcome for us, is poorly understood. We currently focus on two experimental systems: Chlamydia trachomatis infections are responsible for the bulk of sexually transmitted ba
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