RT Journal Article
SR Electronic
T1 A 5’ UTR G-quadruplex controls localisation and translation of a potassium leak channel mRNA
JF bioRxiv
FD Cold Spring Harbor Laboratory
SP 797423
DO 10.1101/797423
A1 Connor J. Maltby
A1 James P. R. Schofield
A1 Steven D. Houghton
A1 Ita O’Kelly
A1 Mariana Vargas-Caballero
A1 Katrin Deinhardt
A1 Mark J. Coldwell
YR 2019
UL http://biorxiv.org/content/early/2019/10/10/797423.abstract
AB RNA G-quadruplexes (G4s) are non-canonical secondary structures that have been proposed to function as regulators of post-transcriptional mRNA localisation and translation. G4s within 3’ UTRs of some neuronal mRNAs are known to control their distal localisation and local translation, contributing to the distinct local proteomes that facilitate the synaptic remodelling attributed to normal cellular function. In this study, we characterise the G4 formation of a (GGN)13 repeat found within the 5’ UTR of KCNK9 mRNA, encoding the potassium 2-pore domain leak channel Task3. Using circular dichroism, we show that this (GGN)13 repeat forms a parallel G4 that exhibits the stereotypical potassium specificity of a G4, remaining thermostable under physiological ionic conditions. The G4 is inhibitory to translation of Task3, which can be overcome through the activity of the G4-specific helicase DHX36, consequently increasing K+ leak currents and decreasing resting membrane potentials in HEK293 cells. Additionally, we observe that this G4 is fundamental to ensuring the delivery of Task3 mRNA to distal primary cortical neurites. It has previously been shown that abnormal Task3 expression correlates with neuronal dysfunction, we therefore posit that this G4 is required for regulated local expression of Task3 leak channels that maintain K+ leak currents within neurons.