Controlling small guanine-nucleotide-exchange factor function through cytoplasmic RNA intramers

Proceedings of the National Academy of Sciences of the United States of America
G MayerMichael Famulok

Abstract

ADP-ribosylation factor (ARF) GTPases and their regulatory proteins have been implicated in the control of diverse biological functions. Two main classes of positive regulatory elements for ARF have been discovered so far: the large Sec7/Gea and the small cytohesin/ARNO families, respectively. These proteins harbor guanine-nucleotide-exchange factor (GEF) activity exerted by the common Sec7 domain. The availability of a specific inhibitor, the fungal metabolite brefeldin A, has enabled documentation of the involvement of the large GEFs in vesicle transport. However, because of the lack of such tools, the biological roles of the small GEFs have remained controversial. Here, we have selected a series of RNA aptamers that specifically recognize the Sec7 domain of cytohesin 1. Some aptamers inhibit guanine-nucleotide exchange on ARF1, thereby preventing ARF activation in vitro. Among them, aptamer M69 exhibited unexpected specificity for the small GEFs, because it does not interact with or inhibit the GEF activity of the related Gea2-Sec7 domain, a member of the class of large GEFs. The inhibitory effect demonstrated in vitro clearly is observed as well in vivo, based on the finding that M69 produces similar results as a dominant-n...Continue Reading

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Citations

Jan 8, 2005·Chembiochem : a European Journal of Chemical Biology·Michael Famulok, Günter Mayer
Nov 12, 2005·Applied Microbiology and Biotechnology·Daniela ProskeAnsgar Resch
Jun 13, 2013·Bioorganic & Medicinal Chemistry·Björn NiebelMichael Famulok
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Jan 28, 2003·Drug Discovery Today·Petra BurgstallerMichael Blind
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Jul 28, 2004·Proceedings of the National Academy of Sciences of the United States of America·Mirko G TheisMichael Famulok
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Dec 6, 2006·Angewandte Chemie·Günter MayerMichael Famulok
Jul 4, 2009·Chembiochem : a European Journal of Chemical Biology·Günter MayerMichael Blind
Aug 7, 2010·Chemistry : a European Journal·Björn NiebelMichael Famulok

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