RNAs that bind and change the permeability of phospholipid membranes.
The RNA world hypothesis presumes that RNA will be competent for varied essential cellular functions. One such indispensable cell function is regulation of membrane permeability. Though this was not a known RNA activity, selection-amplification yielded RNAs that bound phosphatidylcholine:cholesterol liposomes. At least eight distinct, approximately 95-mer sequences bind well to the outside of the lipid bilayer, though randomized sequences had no such activity. No distinct sequence motif for lipid binding was found. However, truncation of one such RNA shows that a smaller, 44-nucleotide irregular RNA hairpin is an active membrane binding domain. Bound RNA increases the permeability of liposomes to (22)Na(+). In addition, using voltage clamp technique, four individual RNAs increase the ion permeability of the plasma membrane of cultured human cells. The existence of multiple sequences that bind membranes and provoke permeability changes suggests that these may be elementary RNA functions that could be selected in vivo.
Khvorova
A
A
Department of Molecular, Cellular, and Developmental Biology, University of Colorado, Boulder, CO 80309-0347, USA.
Kwak
Y G
YG
Tamkun
M
M
Majerfeld
I
I
Yarus
M
M
D001483:Base Sequence; D001665:Binding Sites; D002460:Cell Line; D002463:Cell Membrane Permeability; D002794:Choline / Q000378:metabolism; D002850:Chromatography, Gel; D006801:Humans; D008051:Lipid Bilayers / Q000378:metabolism*; D008081:Liposomes / Q000378:metabolism; D008564:Membrane Potentials; D008567:Membranes, Artificial; D008969:Molecular Sequence Data; D009690:Nucleic Acid Conformation; D009841:Oligonucleotides / Q000378:metabolism; D018408:Patch-Clamp Techniques; D010743:Phospholipids / Q000378:metabolism*; D012313:RNA / Q000378:metabolism* / Q000502:physiology*; D006163:Ribonuclease T1 / Q000378:metabolism; D012979:Sodium Radioisotopes / Q000378:metabolism; D013997:Time Factors; D014158:Transcription, Genetic
D008051:Lipid Bilayers; D008081:Liposomes; D008567:Membranes, Artificial; D009841:Oligonucleotides; D010743:Phospholipids; D012979:Sodium Radioisotopes; D012313:RNA; D006163:Ribonuclease T1; D002794:Choline