Nonsense-Mediated Decay Restricts LncRNA Levels in Yeast Unless Blocked by Double-Stranded RNA Structure

Overview

Journal Mol Cell

Publisher Cell Press

Specialty Cell Biology

Date 2016 Jan 26

PMID 26805575

Citations 61

Authors

Maxime Wery

Marc Descrimes

Nicolas Vogt

Anne-Sophie Dallongeville

Daniel Gautheret

Antonin Morillon

Affiliations

Soon will be listed here.

Abstract

Antisense long non-coding (aslnc)RNAs represent a substantial part of eukaryotic transcriptomes that are, in yeast, controlled by the Xrn1 exonuclease. Nonsense-Mediated Decay (NMD) destabilizes the Xrn1-sensitive aslncRNAs (XUT), but what determines their sensitivity remains unclear. We report that 3' single-stranded (3'-ss) extension mediates XUTs degradation by NMD, assisted by the Mtr4 and Dbp2 helicases. Single-gene investigation, genome-wide RNA analyses, and double-stranded (ds)RNA mapping revealed that 3'-ss extensions discriminate the NMD-targeted XUTs from stable lncRNAs. Ribosome profiling showed that XUT are translated, locking them for NMD activity. Interestingly, mutants of the Mtr4 and Dbp2 helicases accumulated XUTs, suggesting that dsRNA unwinding is a critical step for degradation. Indeed, expression of anticomplementary transcripts protects cryptic intergenic lncRNAs from NMD. Our results indicate that aslncRNAs form dsRNA that are only translated and targeted to NMD if dissociated by Mtr4 and Dbp2. We propose that NMD buffers genome expression by discarding pervasive regulatory transcripts.

Citing Articles

Transcriptome-Wide Analysis of the 5' Cap Status of RNA Using 5' Monophosphate-Dependent Exonuclease Digestion and RNA Sequencing.

Wery M, Szachnowski U, Andjus S, Morillon A Methods Mol Biol. 2024; 2863:117-135.

PMID: 39535708 DOI: 10.1007/978-1-0716-4176-7_9.

Northern Blotting: Protocols for Radioactive and Nonradioactive Detection of RNA.

Wery M, Foretek D, Andjus S, Verdys P, Morillon A Methods Mol Biol. 2024; 2863:13-28.

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Accurate and sensitive interactome profiling using a quantitative protein-fragment complementation assay.

Lazarewicz N, Le Dez G, Cerjani R, Runeshaw L, Meurer M, Knop M Cell Rep Methods. 2024; 4(10):100880.

PMID: 39437715 PMC: 11573789. DOI: 10.1016/j.crmeth.2024.100880.

dsRNA formation leads to preferential nuclear export and gene expression.

Coban I, Lamping J, Hirsch A, Wasilewski S, Shomroni O, Giesbrecht O Nature. 2024; 631(8020):432-438.

PMID: 38898279 PMC: 11236707. DOI: 10.1038/s41586-024-07576-w.

Pervasive translation of Xrn1-sensitive unstable long noncoding RNAs in yeast.

Andjus S, Szachnowski U, Vogt N, Gioftsidi S, Hatin I, Cornu D RNA. 2024; 30(6):662-679.

PMID: 38443115 PMC: 11098462. DOI: 10.1261/rna.079903.123.

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