Pervasive transcription of mammalian genomes leads to a previously underestimated level of complexity in gene regulatory networks. Recently, we have identified a new functional class of natural and synthetic antisense long non-coding RNAs (lncRNA) that increases translation of partially overlapping sense mRNAs. These molecules were named SINEUPs, as they require an embedded inverted SINE B2 element for their UP-regulation of translation. Mouse AS Uchl1 is the representative member of natural SINEUPs. It was originally discovered for its role in increasing translation of Uchl1 mRNA, a gene associated with neurodegenerative diseases. Here we present the secondary structure of the SINE B2 Transposable Element (TE) embedded in AS Uchl1. We find that specific structural regions, containing a short hairpin, are required for the ability of AS Uchl1 RNA to increase translation of its target mRNA. We also provide a high-resolution structure of the relevant hairpin, based on NMR observables. Our results highlight the importance of structural determinants in embedded TEs for their activity as functional domains in lncRNAs.
|Titolo:||Structural determinants of the SINE B2 element embedded in the long non-coding RNA activator of translation AS Uchl1|
|Autori:||Podbevšek, Peter; Fasolo, Francesca; Bon, Carlotta; Cimatti, Laura; Reißer, Sabine; Carninci, Piero; Bussi, Giovanni; Zucchelli, Silvia; Plavec, Janez; Gustincich, Stefano|
|Data di pubblicazione:||2018|
|Numero di Articolo:||3189|
|Digital Object Identifier (DOI):||10.1038/s41598-017-14908-6|
|Fulltext via DOI:||10.1038/s41598-017-14908-6|
|Appare nelle tipologie:||1.1 Journal article|