From Yeast to Mammals, the Nonsense-Mediated MRNA Decay As a Master Regulator of Long Non-Coding RNAs Functional Trajectory

Overview

Journal Noncoding RNA

Date 2021 Aug 27

PMID 34449682

Citations 15

Authors

Sara Andjus

Antonin Morillon

Maxime Wery

Affiliations

Soon will be listed here.

Abstract

The Nonsense-Mediated mRNA Decay (NMD) has been classically viewed as a translation-dependent RNA surveillance pathway degrading aberrant mRNAs containing premature stop codons. However, it is now clear that mRNA quality control represents only one face of the multiple functions of NMD. Indeed, NMD also regulates the physiological expression of normal mRNAs, and more surprisingly, of long non-coding (lnc)RNAs. Here, we review the different mechanisms of NMD activation in yeast and mammals, and we discuss the molecular bases of the NMD sensitivity of lncRNAs, considering the functional roles of NMD and of translation in the metabolism of these transcripts. In this regard, we describe several examples of functional micropeptides produced from lncRNAs. We propose that translation and NMD provide potent means to regulate the expression of lncRNAs, which might be critical for the cell to respond to environmental changes.

Citing Articles

Unlocking the secrets of the immunopeptidome: MHC molecules, ncRNA peptides, and vesicles in immune response.

Balakrishnan A, Winiarek G, Holowka O, Godlewski J, Bronisz A Front Immunol. 2025; 16:1540431.

PMID: 39944685 PMC: 11814183. DOI: 10.3389/fimmu.2025.1540431.

RNA Decay Assay: 5-Ethynyl-Uridine Labeling and Chasing.

Gupta H, Lee J, Hoffman K, Min K, Yoon J Methods Mol Biol. 2024; 2863:139-149.

PMID: 39535709 DOI: 10.1007/978-1-0716-4176-7_10.

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.

LncRNA MALAT1 to Enhance Pyroptosis in Viral Myocarditis Through UPF1-Mediated SIRT6 mRNA Decay and Wnt-β-Catenin Signal Pathway.

Zeng M, Chen Z, Wang Y, Yang Z, Xiang J, Wang X Cardiovasc Toxicol. 2024; 24(12):1439-1454.

PMID: 39367210 DOI: 10.1007/s12012-024-09922-w.

Structure of the Nmd4-Upf1 complex supports conservation of the nonsense-mediated mRNA decay pathway between yeast and humans.

Barbarin-Bocahu I, Ulryck N, Rigobert A, Ruiz Gutierrez N, Decourty L, Raji M PLoS Biol. 2024; 22(9):e3002821.

PMID: 39331656 PMC: 11463774. DOI: 10.1371/journal.pbio.3002821.

References

Huang J, Chen M, Chen D, Gao X, Zhu S, Huang H . A Peptide Encoded by a Putative lncRNA HOXB-AS3 Suppresses Colon Cancer Growth. Mol Cell. 2017; 68(1):171-184.e6. DOI: 10.1016/j.molcel.2017.09.015. View

Bi P, Ramirez-Martinez A, Li H, Cannavino J, McAnally J, Shelton J . Control of muscle formation by the fusogenic micropeptide myomixer. Science. 2017; 356(6335):323-327. PMC: 5502127. DOI: 10.1126/science.aam9361. View

Usuki F, Yamashita A, Fujimura M . Environmental stresses suppress nonsense-mediated mRNA decay (NMD) and affect cells by stabilizing NMD-targeted gene expression. Sci Rep. 2019; 9(1):1279. PMC: 6362056. DOI: 10.1038/s41598-018-38015-2. View

Singh G, Rebbapragada I, Lykke-Andersen J . A competition between stimulators and antagonists of Upf complex recruitment governs human nonsense-mediated mRNA decay. PLoS Biol. 2008; 6(4):e111. PMC: 2689706. DOI: 10.1371/journal.pbio.0060111. View

Smith J, Baker K . Nonsense-mediated RNA decay--a switch and dial for regulating gene expression. Bioessays. 2015; 37(6):612-23. PMC: 4454373. DOI: 10.1002/bies.201500007. View

Brar G, Yassour M, Friedman N, Regev A, Ingolia N, Weissman J . High-resolution view of the yeast meiotic program revealed by ribosome profiling. Science. 2011; 335(6068):552-7. PMC: 3414261. DOI: 10.1126/science.1215110. View

Kunz J, Neu-Yilik G, Hentze M, Kulozik A, Gehring N . Functions of hUpf3a and hUpf3b in nonsense-mediated mRNA decay and translation. RNA. 2006; 12(6):1015-22. PMC: 1464862. DOI: 10.1261/rna.12506. View

Metzstein M, Krasnow M . Functions of the nonsense-mediated mRNA decay pathway in Drosophila development. PLoS Genet. 2007; 2(12):e180. PMC: 1756896. DOI: 10.1371/journal.pgen.0020180. View

Bazzini A, Johnstone T, Christiano R, Mackowiak S, Obermayer B, Fleming E . Identification of small ORFs in vertebrates using ribosome footprinting and evolutionary conservation. EMBO J. 2014; 33(9):981-93. PMC: 4193932. DOI: 10.1002/embj.201488411. View

10.

DLima N, Ma J, Winkler L, Chu Q, Loh K, Corpuz E . A human microprotein that interacts with the mRNA decapping complex. Nat Chem Biol. 2016; 13(2):174-180. PMC: 5247292. DOI: 10.1038/nchembio.2249. View

11.

Wery M, Descrimes M, Vogt N, Dallongeville A, Gautheret D, Morillon A . Nonsense-Mediated Decay Restricts LncRNA Levels in Yeast Unless Blocked by Double-Stranded RNA Structure. Mol Cell. 2016; 61(3):379-392. PMC: 4747904. DOI: 10.1016/j.molcel.2015.12.020. View

12.

Cui Y, Hagan K, Zhang S, Peltz S . Identification and characterization of genes that are required for the accelerated degradation of mRNAs containing a premature translational termination codon. Genes Dev. 1995; 9(4):423-36. DOI: 10.1101/gad.9.4.423. View

13.

Makarewich C, Olson E . Mining for Micropeptides. Trends Cell Biol. 2017; 27(9):685-696. PMC: 5565689. DOI: 10.1016/j.tcb.2017.04.006. View

14.

Gregersen L, Schueler M, Munschauer M, Mastrobuoni G, Chen W, Kempa S . MOV10 Is a 5' to 3' RNA helicase contributing to UPF1 mRNA target degradation by translocation along 3' UTRs. Mol Cell. 2014; 54(4):573-85. DOI: 10.1016/j.molcel.2014.03.017. View

15.

Carter M, Doskow J, Morris P, Li S, Nhim R, Sandstedt S . A regulatory mechanism that detects premature nonsense codons in T-cell receptor transcripts in vivo is reversed by protein synthesis inhibitors in vitro. J Biol Chem. 1995; 270(48):28995-9003. DOI: 10.1074/jbc.270.48.28995. View

16.

Yepiskoposyan H, Aeschimann F, Nilsson D, Okoniewski M, Muhlemann O . Autoregulation of the nonsense-mediated mRNA decay pathway in human cells. RNA. 2011; 17(12):2108-18. PMC: 3222124. DOI: 10.1261/rna.030247.111. View

17.

Johns L, Grimson A, Kuchma S, Newman C, Anderson P . Caenorhabditis elegans SMG-2 selectively marks mRNAs containing premature translation termination codons. Mol Cell Biol. 2007; 27(16):5630-8. PMC: 1952128. DOI: 10.1128/MCB.00410-07. View

18.

Harigaya Y, Parker R . No-go decay: a quality control mechanism for RNA in translation. Wiley Interdiscip Rev RNA. 2011; 1(1):132-41. DOI: 10.1002/wrna.17. View

19.

Mishra S, Wang H . Computational Analysis Predicts Hundreds of Coding lncRNAs in Zebrafish. Biology (Basel). 2021; 10(5). PMC: 8145020. DOI: 10.3390/biology10050371. View

20.

Alexandrov A, Colognori D, Steitz J . Human eIF4AIII interacts with an eIF4G-like partner, NOM1, revealing an evolutionarily conserved function outside the exon junction complex. Genes Dev. 2011; 25(10):1078-90. PMC: 3093123. DOI: 10.1101/gad.2045411. View