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Determination of in vivo target search kinetics of regulatory noncoding RNA

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Science  20 Mar 2015:
Vol. 347, Issue 6228, pp. 1371-1374
DOI: 10.1126/science.1258849

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RNA kinetics may define regulatory hierarchy

The double-helical structure of DNA suggests immediately how nucleic acid polymers can recognize and bind to homologous sequences. Target recognition by RNA is vital in many biological processes. Fei et al. used super-resolution microscopy of tagged RNAs and computer modeling to understand how RNA-RNA base-pairing reactions occur in vivo. They studied a small RNA (sRNA) that targets a messenger RNA (mRNA) for degradation in bacteria. They observed a slow rate of association as the sRNA searched for its mRNA target, but thereafter a fast rate of dissociation. This explains the need for high concentrations of sRNA to cause mRNA degradation. The sRNA found different target mRNAs at different rates, allowing the generation of a regulatory hierarchy.

Science, this issue p. 1371

Abstract

Base-pairing interactions between nucleic acids mediate target recognition in many biological processes. We developed a super-resolution imaging and modeling platform that enabled the in vivo determination of base pairing–mediated target recognition kinetics. We examined a stress-induced bacterial small RNA, SgrS, which induces the degradation of target messenger RNAs (mRNAs). SgrS binds to a primary target mRNA in a reversible and dynamic fashion, and formation of SgrS-mRNA complexes is rate-limiting, dictating the overall regulation efficiency in vivo. Examination of a secondary target indicated that differences in the target search kinetics contribute to setting the regulation priority among different target mRNAs. This super-resolution imaging and analysis approach provides a conceptual framework that can be generalized to other small RNA systems and other target search processes.

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