RNA Folding

Determining how RNA (ribonucleic acid) folds, or "ravels", may offer a key to un-raveling how and why anomalies occur in the human genome. RNA is now known to play a pivotal role in gene silencing, gene shuffling, protein regulation and disease. However in contrast to proteins, very little is known about how RNA takes its three-dimensional shape and under certain circumstances works as an enzyme. Getting a good look at RNA in the process of folding from its initial 1-D "ribbon" state, into a 3-D "knot" (the form in which RNA is biologically functional) would be very valuable information. Enter SAXS (small angle x-ray scattering), an effective tool for time-resolved studies of structural changes which does not require crystals. A group of researchers from Stanford University have used SAXS to study the process of RNA folding in real time utilizing the SAXS synchrotron beam line at SSRL. Using SAXS, in combination with stopped-flow and continuous-flow kinetics, the researchers have directly monitored for the first time the RNA chain compaction that occurs during folding. This was done in order to determine whether compaction occurs as an early step in folding, before specific tertiary (final) structure formation, or whether it occurs as long-range contacts form. They found that RNA forms a nonspecifically collapsed intermediate shape and then searches for its final contacts within a highly structured subset of conformational space, and that RNA folding is highly path-dependent.

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(click on image for larger view) Science Highlight Herschlag Faculty Page Doniach Faculty Page SAXS at SSRL		March 2003
		Exploring the Folding Landscape of a Structured RNA by SAXS Rick Russell, Ian S. Millett, Sebastian Doniach and Daniel Herschlag, Stanford University


		Determining how RNA (ribonucleic acid) folds, or "ravels", may offer a key to un-raveling how and why anomalies occur in the human genome. RNA is now known to play a pivotal role in gene silencing, gene shuffling, protein regulation and disease. However in contrast to proteins, very little is known about how RNA takes its three-dimensional shape and under certain circumstances works as an enzyme. Getting a good look at RNA in the process of folding from its initial 1-D "ribbon" state, into a 3-D "knot" (the form in which RNA is biologically functional) would be very valuable information. Enter SAXS (small angle x-ray scattering), an effective tool for time-resolved studies of structural changes which does not require crystals. A group of researchers from Stanford University have used SAXS to study the process of RNA folding in real time utilizing the SAXS synchrotron beam line at SSRL. Using SAXS, in combination with stopped-flow and continuous-flow kinetics, the researchers have directly monitored for the first time the RNA chain compaction that occurs during folding. This was done in order to determine whether compaction occurs as an early step in folding, before specific tertiary (final) structure formation, or whether it occurs as long-range contacts form. They found that RNA forms a nonspecifically collapsed intermediate shape and then searches for its final contacts within a highly structured subset of conformational space, and that RNA folding is highly path-dependent.