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ScienceDaily_2014 00524.txt

#Live and let-7: microrna plays surprising role in cell survival Researchers at the University of California San diego School of medicine have identified a microrna molecule as a surprisingly crucial player in managing cell survival and growth. The findings published in the October 7 issue of Cell Metabolism underscore the emerging recognition that non-coding RNAS small molecules that are translated not into working proteins help regulate basic cellular processes and may be key to developing new drugs and therapies. Specifically principal investigator Albert R. La Spada MD Phd professor of cellular and molecular medicine chief of the Division of Genetics in the Department of Pediatrics and associate director of the Institute for Genomic Medicine at UC San diego and colleagues found that a microrna known as let-7 controls autophagy through the amino acid sensing pathway which has emerged as the most potent activator of mtorc1 complex activity. Autophagy is a fundamental process used by cells to degrade unnecessary components in times of starvation releasing energy stores that help promote cell survival. Cells have adapted further autophagy for other purposes as well including recycling dysfunctional components immune response to pathogen invasion surveillance against cancer and maintenance of protein and organelle control in the central nervous system. MTORC1 is a critical protein complex that regulates energy consumption and growth in cells. he ability of let-7 alone to activate autophagy in this way was totally unknown and is very surprisingsaid La Spada. s let-7 is known to be a tumor suppressor its ability to activate autophagy could be a major component of its anti-tumor forming activitythough La Spada noted that autophagy may also contrarily promote tumor progression by supporting the altered metabolism of growing cancers. With let-7 revealed to be a master regulator of metabolism helping to modulate anabolic growth (the creation of new molecules in cells) with catabolic destruction (the breakdown of molecules in cells) researchers say the overall picture of how cells function becomes more fine-tuned but also more complicated. he fact that let-7 is opposing the action of the amino acid sensing pathway provides a glimpse into the complex pathway regulation at work in the cell with micrornas emerging as important factors for cells to maintain metabolic set points and overall homeostasis or a healthy equilibrium. he therapeutic potential of let-7 remains to be explored. La Spada said he and colleagues have shown that a lentivirus encoding let-7 injected into mouse neurons promotes the autophagic turnover of toxic misfolded proteins associated with neurodegenerative disease. e also demonstrate that treatment with anti-let-7 can block autophagy and that this has physiological consequences (weight gain) in mice. It is possible that modulation of let-7 could be pursued for therapeutic application using very carefully targeted delivery systems but further work will be necessary to see if this is practically possible. tory Source: The above story is provided based on materials by University of California San diego Health Sciences. Note: Materials may be edited for content and length. Journal Reference g

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