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.

Structural determinants of the SINE B2 element embedded in the long non-coding RNA activator of translation AS Uchl1 / Podbevšek, Peter; Fasolo, Francesca; Bon, Carlotta; Cimatti, Laura; Reißer, Sabine; Carninci, Piero; Bussi, Giovanni; Zucchelli, Silvia; Plavec, Janez; Gustincich, Stefano. - In: SCIENTIFIC REPORTS. - ISSN 2045-2322. - 8:1(2018), pp. 1-13. [10.1038/s41598-017-14908-6]

Structural determinants of the SINE B2 element embedded in the long non-coding RNA activator of translation AS Uchl1

Podbevšek, Peter;Fasolo, Francesca;Bon, Carlotta;Cimatti, Laura;Reißer, Sabine;Bussi, Giovanni;Zucchelli, Silvia;Gustincich, Stefano
2018

Abstract

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.
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10.1038/s41598-017-14908-6
Podbevšek, Peter; Fasolo, Francesca; Bon, Carlotta; Cimatti, Laura; Reißer, Sabine; Carninci, Piero; Bussi, Giovanni; Zucchelli, Silvia; Plavec, Janez; Gustincich, Stefano
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/20.500.11767/67664
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