Abstract
Biological RNAs that bind small molecules have been implicated in a variety of regulatory and catalytic processes. Inspired by these examples, we used in vitro selection to search a pool of genome-encoded RNA fragments for naturally occurring GTP aptamers. Several aptamer classes were identified, including one (the "G motif") with a G-quadruplex structure. Further analysis revealed that most RNA and DNA G-quadruplexes bind GTP. The G motif is abundant in eukaryotes, and the human genome contains ~75,000 examples with dissociation constants comparable to the GTP concentration of a eukaryotic cell (~300 μM). G-quadruplexes play roles in diverse cellular processes, and our findings raise the possibility that GTP may play a role in the function of these elements. Consistent with this possibility, the sequence requirements of several classes of regulatory G-quadruplexes parallel those of GTP binding.
Highlights
Once thought to function primarily as a passive carrier of genetic information, RNA is known to play an active role in diverse cellular processes (Tucker and Breaker, 2005; Huttenhofer et al, 2005; Bartel, 2009; Zhang et al, 2009)
The role of RNA-bound small molecules is to modulate RNA folding in a manner that regulates gene expression (Tucker and Breaker, 2005)
In the presence of thiamine, the 5' untranslated region of the E. coli thiC mRNA adopts a secondary structure in which its Shine-Dalgarno sequence is inaccessible to the ribosome, resulting in decreased expression of downstream genes (Winkler et al, 2002)
Summary
Biological RNAs that bind small-molecules have been implicated in a variety of regulatory and catalytic processes. Inspired by these examples, we used in vitro selection to search a pool of genomeencoded RNA fragments for naturally occurring GTP aptamers. Several classes of aptamers were identified, including one ("the G motif") with a G-quadruplex structure. G-quadruplexes play roles in diverse cellular processes, and our findings raise the possibility that GTP may play a role in the function of these elements. Consistent with this possibility, the sequence requirements of several classes of regulatory G-quadruplexes parallel those of GTP binding
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