RT Journal Article
T1 MicroRNA 199a-5p Attenuates Retrograde Transport and Protects against Toxin-Induced Inhibition of Protein Biosynthesis
A1 Aranda Gómez, Juan Francisco
A1 Rathjen, Stefan
A1 Johannes, Ludger
A1 Fernández-Hernando, Carlos
AB Retrograde transport (RT) allows cells to retrieve receptors and other cellular cargoes for delivery to the Golgi apparatus, contributing to the maintenance of cellular homeostasis. This transport route is also commonly used by several bacterial toxins to exert their deleterious actions on eukaryotic cells. While the retrograde transport process has been well characterized, the contribution of microRNAs (miRNAs) in regulating this cellular transport mechanism remains unknown. Here, we determined that mir-199a and mir-199b, members of the intronic miRNA family, coordinate genes regulating RT and endosome trafficking. We demonstrate that miR-199a-5p attenuates the expression of Vps26A, Rab9B, and M6PR, thereby controlling RT from endosomes to the trans-Golgi network (TGN). Importantly, we found that overexpression of a Vps26A construct resistant to the inhibitory action of miR-199a-5p abrogates the effect of miR-199a-5p on RT. Finally, we demonstrate that miR-199-5p overexpression attenuates Shiga toxin type 1 (Stx1)-mediated inhibition of protein biosynthesis. In summary, our work identifies the first noncoding RNA that influences RT and reduces the inhibition of protein biosynthesis caused by bacterial toxins.
PB Taylor & Francis
SN 0270-7306
YR 2018
FD 2018
LK https://hdl.handle.net/20.500.14352/94489
UL https://hdl.handle.net/20.500.14352/94489
LA eng
NO Aranda, J. F., Rathjen, S., Johannes, L., & Fernández-Hernando, C. (2018). MicroRNA 199a-5p Attenuates Retrograde Transport and Protects against Toxin-Induced Inhibition of Protein Biosynthesis. Molecular and Cellular Biology, 38(11). https://doi.org/10.1128/MCB.00548-17
NO ACKNOWLEDGMENTSWe thank Juan Bonifacino for generously providing the Vps26A-GFP and M6PR-GFP plasmids. We also thank Carlos Estella for critical discussions and comments about this work.This work was supported by grants from the National Institutes of Health, R35HL135820 to C.F.-H., the Foundation Leducq (MIRVAD network) to C.F.-H., and American Heart Association Established Investigator award (16EIA27550004) to C.F.-H.
NO National Institutes of Health
NO Foundation Leducq
NO American Heart Association
DS Docta Complutense
RD 8 jun 2026