Nonsense-mediated MRNA Decay: a 'nonsense' Pathway Makes Sense in Stem Cell Biology

Overview

Journal Nucleic Acids Res

Publisher Oxford University Press

Specialty Biochemistry

Date 2017 Dec 23

PMID 29272451

Citations 25

Authors

Xin Han

Yanling Wei

Hua Wang

Feilong Wang

Zhenyu Ju

Tangliang Li

Affiliations

Soon will be listed here.

Abstract

Nonsense-mediated mRNA decay (NMD) is a highly conserved post-transcriptional regulatory mechanism of gene expression in eukaryotes. Originally, NMD was identified as an RNA surveillance machinery in degrading 'aberrant' mRNA species with premature termination codons. Recent studies indicate that NMD regulates the stability of natural gene transcripts that play significant roles in cell functions. Although components and action modes of the NMD machinery in degrading its RNA targets have been extensively studied with biochemical and structural approaches, the biological roles of NMD remain to be defined. Stem cells are rare cell populations, which play essential roles in tissue homeostasis and hold great promises in regenerative medicine. Stem cells self-renew to maintain the cellular identity and differentiate into somatic lineages with specialized functions to sustain tissue integrity. Transcriptional regulations and epigenetic modulations have been extensively implicated in stem cell biology. However, post-transcriptional regulatory mechanisms, such as NMD, in stem cell regulation are largely unknown. In this paper, we summarize the recent findings on biological roles of NMD factors in embryonic and tissue-specific stem cells. Furthermore, we discuss the possible mechanisms of NMD in regulating stem cell fates.

Citing Articles

Fine-tuning of Wnt signaling by RNA surveillance factor Smg5 in the mouse craniofacial development.

Zhu S, Huo S, He W, Huang C, Zhang J, Jiang X iScience. 2025; 28(3):111972.

PMID: 40071146 PMC: 11894330. DOI: 10.1016/j.isci.2025.111972.

RNA Surveillance Factor SMG5 Is Essential for Mouse Embryonic Stem Cell Differentiation.

Chen C, Wei Y, Jiang X, Li T Biomolecules. 2024; 14(8).

PMID: 39199410 PMC: 11352633. DOI: 10.3390/biom14081023.

UPF3B modulates endoplasmic reticulum stress through interaction with inositol-requiring enzyme-1α.

Sun X, Lin R, Lu X, Wu Z, Qi X, Jiang T Cell Death Dis. 2024; 15(8):587.

PMID: 39138189 PMC: 11322666. DOI: 10.1038/s41419-024-06973-3.

Alternative splicing coupled to nonsense-mediated decay coordinates downregulation of non-neuronal genes in developing mouse neurons.

Zhuravskaya A, Yap K, Hamid F, Makeyev E Genome Biol. 2024; 25(1):162.

PMID: 38902825 PMC: 11188260. DOI: 10.1186/s13059-024-03305-8.

A Canadian Survey of Research on HIV-1 Latency-Where Are We Now and Where Are We Heading?.

Abdalla A, Guajardo-Contreras G, Mouland A Viruses. 2024; 16(2).

PMID: 38400005 PMC: 10891605. DOI: 10.3390/v16020229.

References

Mikkola H, Orkin S . The journey of developing hematopoietic stem cells. Development. 2006; 133(19):3733-44. DOI: 10.1242/dev.02568. View

Colak D, Ji S, Porse B, Jaffrey S . Regulation of axon guidance by compartmentalized nonsense-mediated mRNA decay. Cell. 2013; 153(6):1252-65. PMC: 3685487. DOI: 10.1016/j.cell.2013.04.056. View

Nelson J, Moore K, Chapin A, Hollien J, Metzstein M . Degradation of Gadd45 mRNA by nonsense-mediated decay is essential for viability. Elife. 2016; 5. PMC: 4848089. DOI: 10.7554/eLife.12876. View

Bao J, Tang C, Yuan S, Porse B, Yan W . UPF2, a nonsense-mediated mRNA decay factor, is required for prepubertal Sertoli cell development and male fertility by ensuring fidelity of the transcriptome. Development. 2014; 142(2):352-62. PMC: 4302838. DOI: 10.1242/dev.115642. View

Ajamian L, Abel K, Rao S, Vyboh K, Garcia-de-Gracia F, Soto-Rifo R . HIV-1 Recruits UPF1 but Excludes UPF2 to Promote Nucleocytoplasmic Export of the Genomic RNA. Biomolecules. 2015; 5(4):2808-39. PMC: 4693258. DOI: 10.3390/biom5042808. View

Balistreri G, Bognanni C, Muhlemann O . Virus Escape and Manipulation of Cellular Nonsense-Mediated mRNA Decay. Viruses. 2017; 9(1). PMC: 5294993. DOI: 10.3390/v9010024. View

Azzalin C, Lingner J . The human RNA surveillance factor UPF1 is required for S phase progression and genome stability. Curr Biol. 2006; 16(4):433-9. DOI: 10.1016/j.cub.2006.01.018. View

Liang G, Zhang Y . Embryonic stem cell and induced pluripotent stem cell: an epigenetic perspective. Cell Res. 2012; 23(1):49-69. PMC: 3541668. DOI: 10.1038/cr.2012.175. View

Jolly L, Homan C, Jacob R, Barry S, Gecz J . The UPF3B gene, implicated in intellectual disability, autism, ADHD and childhood onset schizophrenia regulates neural progenitor cell behaviour and neuronal outgrowth. Hum Mol Genet. 2013; 22(23):4673-87. DOI: 10.1093/hmg/ddt315. View

10.

Wu X, Scott D, Kriz A, Chiu A, Hsu P, Dadon D . Genome-wide binding of the CRISPR endonuclease Cas9 in mammalian cells. Nat Biotechnol. 2014; 32(7):670-6. PMC: 4145672. DOI: 10.1038/nbt.2889. View

11.

Nickless A, Jackson E, Marasa J, Nugent P, Mercer R, Piwnica-Worms D . Intracellular calcium regulates nonsense-mediated mRNA decay. Nat Med. 2014; 20(8):961-6. PMC: 4126864. DOI: 10.1038/nm.3620. View

12.

Keller G . Embryonic stem cell differentiation: emergence of a new era in biology and medicine. Genes Dev. 2005; 19(10):1129-55. DOI: 10.1101/gad.1303605. View

13.

Snow B, Erdmann N, Cruickshank J, Goldman H, Gill R, Robinson M . Functional conservation of the telomerase protein Est1p in humans. Curr Biol. 2003; 13(8):698-704. DOI: 10.1016/s0960-9822(03)00210-0. View

14.

Karam R, Wengrod J, Gardner L, Wilkinson M . Regulation of nonsense-mediated mRNA decay: implications for physiology and disease. Biochim Biophys Acta. 2013; 1829(6-7):624-33. PMC: 3660545. DOI: 10.1016/j.bbagrm.2013.03.002. View

15.

Zaret K, Grompe M . Generation and regeneration of cells of the liver and pancreas. Science. 2008; 322(5907):1490-4. PMC: 2641009. DOI: 10.1126/science.1161431. View

16.

Park Y, Gerson S . DNA repair defects in stem cell function and aging. Annu Rev Med. 2005; 56:495-508. DOI: 10.1146/annurev.med.56.082103.104546. View

17.

Hockemeyer D, Wang H, Kiani S, Lai C, Gao Q, Cassady J . Genetic engineering of human pluripotent cells using TALE nucleases. Nat Biotechnol. 2011; 29(8):731-4. PMC: 3152587. DOI: 10.1038/nbt.1927. View

18.

Tam P, Loebel D . Gene function in mouse embryogenesis: get set for gastrulation. Nat Rev Genet. 2007; 8(5):368-81. DOI: 10.1038/nrg2084. View

19.

Chawla R, Redon S, Raftopoulou C, Wischnewski H, Gagos S, Azzalin C . Human UPF1 interacts with TPP1 and telomerase and sustains telomere leading-strand replication. EMBO J. 2011; 30(19):4047-58. PMC: 3209776. DOI: 10.1038/emboj.2011.280. View

20.

Azzalin C . UPF1: a leader at the end of chromosomes. Nucleus. 2011; 3(1):16-21. DOI: 10.4161/nucl.18929. View