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Chemical substitution: on early earth, iron may have performedmagnesium's rna folding job by 123wert sdfsf





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Chemical substitution: on early earth, iron may have performedmagnesium's rna folding job by
Article Posted: 12/13/2012
Article Views: 72
Articles Written: 2217
Word Count: 622
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Chemical substitution: on early earth, iron may have performedmagnesium's rna folding job


 
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There is considerable evidence that the evolution of life passedthrough an early stage when RNA played a more central role beforeDNA and coded proteins appeared. During that time, more than 3billion years ago, the environment lacked oxygen but had anabundance of soluble iron. In a new study, researchers from the Georgia Institute ofTechnology used experiments and numerical calculations to show thatiron, in the absence of oxygen, can substitute for magnesium in RNAbinding, folding and catalysis. The researchers found that RNA'sshape and folding structure remained the same and its functionalactivity increased when magnesium was replaced by iron in anoxygen-free environment. "The primary motivation of this work was to understand RNA inplausible early earth conditions and we found that iron couldsupport an array of RNA structures and catalytic functions morediverse than RNA with magnesium," said Loren Williams, aprofessor in the School of Chemistry and Biochemistry at GeorgiaTech.



The results of the study were published online on May 31, 2012 inthe journal PLoS ONE . The study was supported by the NASA Astrobiology Institute. In addition to Williams, Georgia Tech School of Biologypostdoctoral fellow Shreyas Athavale, research scientist AntonPetrov, and professors Roger Wartell and Stephen Harvey, andGeorgia Tech School of Chemistry and Biochemistry postdoctoralfellow Chiaolong Hsiao and professor Nicholas Hud also contributedto this work. Free oxygen gas was almost nonexistent more than 3 billion yearsago in the early earth's atmosphere.



When oxygen began entering theenvironment as a product of photosynthesis, it turned the earth'siron to rust, forming massive banded iron formations that are stillmined today. The free oxygen produced by advanced organisms causediron to be toxic, even though it was -- and still is -- arequirement for life. This environmental transition triggered by the introduction of freeoxygen into the atmosphere would have caused a slow, but dramatic,shift in biology that required transformations in biochemicalmechanisms and metabolic pathways. The current study providesevidence that this transition may have caused a shift from iron tomagnesium for RNA binding, folding and catalysis processes. The researchers used quantum mechanical calculations, chemicalfootprinting and two ribozyme assays to determine that in anoxygen-free environment, iron, Fe2+, can be substituted formagnesium, Mg2+, in RNA folding and catalysis.



Quantum mechanical calculations showed that the structure of RNAwas nearly identical when it included iron or magnesium. When largeRNAs fold into native, stable structures, negatively chargedphosphate groups are brought into close proximity. The researcherscalculated one small difference between the activity of iron andmagnesium structures: more charge was transferred from phosphate toiron than from phosphate to magnesium. Chemical probing under anaerobic conditions showed that iron couldreplace magnesium in compacting and folding large RNA structures,thus providing evidence that iron and magnesium could be nearlyinterchangeable in their interactions with RNA. Under identical anaerobic conditions, the activity of two enzymeswas enhanced in the presence of iron, compared to their activity inthe presence of magnesium.



The initial activity of the L1 ribozymeligase, an enzyme that glues together pieces of RNA, was 25 timeshigher in the presence of iron. Activity of the hammerheadribozyme, an enzyme that cuts RNA, was three times higher in thepresence of iron compared to magnesium. "The results suggest that iron is a superior substitute formagnesium in these catalytic roles," said Williams, who isalso director of the Center for Ribosomal Origins and Evolution atGeorgia Tech. "Our hypothesis is that RNA evolved in thepresence of iron and is optimized to work with iron." In future studies, the researchers plan to investigate what uniquefunctions RNA can possess with iron that are not possible withmagnesium.

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