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The nitrogen regulation stress response is an adaptive mechanism used by nitrogen-starved\n                    <jats:italic>Escherichia coli<\/jats:italic>\n                    to scavenge for alternative nitrogen sources and requires the global transcriptional regulator NtrC. In addition, nitrogen-starved\n                    <jats:italic>E. coli<\/jats:italic>\n                    cells synthesize a signal molecule, guanosine tetraphosphate (ppGpp), which serves as an effector molecule of many processes including transcription to initiate global physiological changes, collectively termed the stringent response. The regulatory mechanisms leading to elevated ppGpp levels during nutritional stresses remain elusive. Here, we show that transcription of\n                    <jats:italic>relA<\/jats:italic>\n                    , a key gene responsible for the synthesis of ppGpp, is activated by NtrC during nitrogen starvation. The results reveal that NtrC couples these two major bacterial stress responses to manage conditions of nitrogen limitation, and provide novel mechanistic insights into how a specific nutritional stress leads to elevating ppGpp levels in bacteria.\n                  <\/jats:p>","DOI":"10.1038\/ncomms5115","type":"journal-article","created":{"date-parts":[[2014,6,20]],"date-time":"2014-06-20T06:57:35Z","timestamp":1403247455000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":181,"title":["Nitrogen stress response and stringent response are coupled in Escherichia coli"],"prefix":"10.1038","volume":"5","author":[{"given":"Daniel R.","family":"Brown","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Geraint","family":"Barton","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhensheng","family":"Pan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Martin","family":"Buck","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sivaramesh","family":"Wigneshweraraj","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2014,6,20]]},"reference":[{"key":"BFncomms5115_CR1","doi-asserted-by":"publisher","first-page":"155","DOI":"10.1146\/annurev.micro.57.030502.090820","volume":"57","author":"L Reitzer","year":"2003","unstructured":"Reitzer, L. 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