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Science in Focus: Jovanka Koo

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The expanding field of small RNA biology in bacteria.

We think of bacteria as non-rational organisms, yet they live in diverse and sometimes extreme environments that range from the surface of the human skin to the high acid of the stomach, from the hot springs of the Yellowstone National Park to the deep sea vents. In these various locales, bacteria have to adjust to constant changes in their surroundings. In the case of the pathogen Salmonella typhimurium, for example, the bacterium reprograms its lifestyle to adapt to the move from contaminated food items such as those in a buffet salad bar to living in the human gastrointestinal tract. This requires making decisions on the molecular level. These bacteria have to determine what genes that they carry in their arsenal will allow them to survive in one environment and which ones they will not need to invest energy in producing in another. To make these often sudden choices, bacteria can use small RNA (sRNA) molecules to control which genes are expressed (or utilized) and which ones are not needed. These decisions can be made at various steps of the genetic information pathway, and for a long time it was thought that only proteins act as these switches.

Chemical cousins of DNA in genes, sRNAs have only recently been identified. As their name suggests, sRNAs are short in length, typically less than 300 nucleotides, and have been identified in virtually all forms of life. They have been associated with processes that regulate development of embryos and the nervous system and even cancer in higher organisms. In bacteria, sRNAs help regulate cell-to-cell communication, disease-inducing pathways, and general response of these organisms to the stresses that they encounter in the environment (for example, heat and cold shock, nutrient starvation).

Hundreds of sRNAs have been found in many bacterial species in just the last several years. One of the most intriguing aspects of sRNA biology in bacteria is their location in the genome. They are located in regions between genes, the regions that used to be thought of as useless ("junk") or silent DNA. The identification of these RNA regulators has benefited from the development of powerful sequencing methodologies and bioinformatics data analysis. We are currently in the golden age of advances in sequencing technologies, and researchers are taking advantage of it. The lowered costs of pyrosequencing and in silico experiments have led to exploration of RNA-omes of organisms. Mapping out all of the RNAs in an organism's repertoire, also known as transcriptomic analysis, is leading up to the possibility of sequencing on the single bacterial cell level in the not-too-distant future.

Recent reports of the global approaches for sRNA identification in numerous bacterial species are revealing that sRNAs play a larger role in the regulation of gene expression than was ever imagined. The questions of what is the sRNA content of a bacterium, which targets the sRNAs control, and by what mechanisms, will be addressed for many years in the future. And in turn, the answers to these questions will offer tantalizing new possibilities to study bacteria that are human pathogens and to detect, cure, and prevent illnesses that they cause. Moreover, the continued explosion in the research on bacterial sRNAs will also be critical in understanding some of the fundamental aspects of life, including how the information about the environment is transferred from outside an organism to the inside.

Jovanka Koo is associate professor of biology at Wheaton College.

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