Nuclear MRNA Decay: Regulatory Networks That Control Gene Expression

Overview

Journal Nat Rev Genet

Specialty Genetics

Date 2024 Apr 18

PMID 38637632

Authors

Xavier Rambout

Lynne E Maquat

Affiliations

Soon will be listed here.

Abstract

Proper regulation of mRNA production in the nucleus is critical for the maintenance of cellular homoeostasis during adaptation to internal and environmental cues. Over the past 25 years, it has become clear that the nuclear machineries governing gene transcription, pre-mRNA processing, pre-mRNA and mRNA decay, and mRNA export to the cytoplasm are inextricably linked to control the quality and quantity of mRNAs available for translation. More recently, an ever-expanding diversity of new mechanisms by which nuclear RNA decay factors finely tune the expression of protein-encoding genes have been uncovered. Here, we review the current understanding of how mammalian cells shape their protein-encoding potential by regulating the decay of pre-mRNAs and mRNAs in the nucleus.

Citing Articles

Identification of Two Elusive Human Ribonuclease MRP-Specific Protein Components.

Che R, Mirani B, Panah M, Chen X, Luo H, Alexandrov A bioRxiv. 2025; .

PMID: 39896489 PMC: 11785048. DOI: 10.1101/2025.01.19.633795.

Cytoplasmic mRNA decay and quality control machineries in eukaryotes.

Dowdle M, Lykke-Andersen J Nat Rev Genet. 2025; .

PMID: 39870755 DOI: 10.1038/s41576-024-00810-1.

Recurrent oncogenic ZC3H18 mutations stabilize endogenous retroviral RNA.

Tanu T, Cox A, Karlow J, Sharma P, He X, Wu C bioRxiv. 2025; .

PMID: 39868094 PMC: 11760258. DOI: 10.1101/2025.01.10.632423.

Gene expression patterns of the LDL receptor and its inhibitor Pcsk9 in the adult zebrafish brain suggest a possible role in neurogenesis.

Gence L, Morello E, Rastegar S, Apalama M, Meilhac O, Bascands J Eur J Neurosci. 2024; 61(1):e16586.

PMID: 39551948 PMC: 11664473. DOI: 10.1111/ejn.16586.

Epigenomic, cistromic, and transcriptomic profiling of primary kidney tubular cells.

Liu Z, Zhang L, Chen Y J Biol Methods. 2024; 11(2):e99010015.

PMID: 39323486 PMC: 11423943. DOI: 10.14440/jbm.2024.0009.

References

Mattout A, Gaidatzis D, Padeken J, Schmid C, Aeschimann F, Kalck V . LSM2-8 and XRN-2 contribute to the silencing of H3K27me3-marked genes through targeted RNA decay. Nat Cell Biol. 2020; 22(5):579-590. PMC: 7212045. DOI: 10.1038/s41556-020-0504-1. View

Lubas M, Andersen P, Schein A, Dziembowski A, Kudla G, Jensen T . The human nuclear exosome targeting complex is loaded onto newly synthesized RNA to direct early ribonucleolysis. Cell Rep. 2015; 10(2):178-92. DOI: 10.1016/j.celrep.2014.12.026. View

Goodarzi H, Zhang S, Buss C, Fish L, Tavazoie S, Tavazoie S . Metastasis-suppressor transcript destabilization through TARBP2 binding of mRNA hairpins. Nature. 2014; 513(7517):256-60. PMC: 4440807. DOI: 10.1038/nature13466. View

Fong J, Pignata L, Goy P, Kawabata K, Chun-Wei Lee S, Koh C . Therapeutic Targeting of RNA Splicing Catalysis through Inhibition of Protein Arginine Methylation. Cancer Cell. 2019; 36(2):194-209.e9. PMC: 7194031. DOI: 10.1016/j.ccell.2019.07.003. View

Insco M, Abraham B, Dubbury S, Kaltheuner I, Dust S, Wu C . Oncogenic mutations impede nuclear RNA surveillance. Science. 2023; 380(6642):eabn7625. PMC: 10184553. DOI: 10.1126/science.abn7625. View

Cevher M, Zhang X, Fernandez S, Kim S, Baquero J, Nilsson P . Nuclear deadenylation/polyadenylation factors regulate 3' processing in response to DNA damage. EMBO J. 2010; 29(10):1674-87. PMC: 2876964. DOI: 10.1038/emboj.2010.59. View

Gordon J, Phizicky D, Neugebauer K . Nuclear mechanisms of gene expression control: pre-mRNA splicing as a life or death decision. Curr Opin Genet Dev. 2020; 67:67-76. PMC: 8084925. DOI: 10.1016/j.gde.2020.11.002. View

Davidson L, Kerr A, West S . Co-transcriptional degradation of aberrant pre-mRNA by Xrn2. EMBO J. 2012; 31(11):2566-78. PMC: 3365414. DOI: 10.1038/emboj.2012.101. View

Li Y, Wang M, Yang M, Xiao Y, Jian Y, Shi D . Nicotine-Induced ILF2 Facilitates Nuclear mRNA Export of Pluripotency Factors to Promote Stemness and Chemoresistance in Human Esophageal Cancer. Cancer Res. 2021; 81(13):3525-3538. DOI: 10.1158/0008-5472.CAN-20-4160. View

10.

de Nadal E, Ammerer G, Posas F . Controlling gene expression in response to stress. Nat Rev Genet. 2011; 12(12):833-45. DOI: 10.1038/nrg3055. View

11.

Kelly S, Leung S, Pak C, Banerjee A, Moberg K, Corbett A . A conserved role for the zinc finger polyadenosine RNA binding protein, ZC3H14, in control of poly(A) tail length. RNA. 2014; 20(5):681-8. PMC: 3988569. DOI: 10.1261/rna.043984.113. View

12.

Dubiez E, Pellegrini E, Finderup Brask M, Garland W, Foucher A, Huard K . Structural basis for competitive binding of productive and degradative co-transcriptional effectors to the nuclear cap-binding complex. Cell Rep. 2024; 43(1):113639. DOI: 10.1016/j.celrep.2023.113639. View

13.

Kim J, Kingston R . Context-specific Polycomb mechanisms in development. Nat Rev Genet. 2022; 23(11):680-695. PMC: 9933872. DOI: 10.1038/s41576-022-00499-0. View

14.

Rosa-Mercado N, Steitz J . Who let the DoGs out? - biogenesis of stress-induced readthrough transcripts. Trends Biochem Sci. 2021; 47(3):206-217. PMC: 8840951. DOI: 10.1016/j.tibs.2021.08.003. View

15.

Tang P, Yang Y, Li G, Huang L, Wen M, Ruan W . Alternative polyadenylation by sequential activation of distal and proximal PolyA sites. Nat Struct Mol Biol. 2022; 29(1):21-31. DOI: 10.1038/s41594-021-00709-z. View

16.

Naro C, Jolly A, Di Persio S, Bielli P, Setterblad N, Alberdi A . An Orchestrated Intron Retention Program in Meiosis Controls Timely Usage of Transcripts during Germ Cell Differentiation. Dev Cell. 2017; 41(1):82-93.e4. PMC: 5392497. DOI: 10.1016/j.devcel.2017.03.003. View

17.

Henriques T, Scruggs B, Inouye M, Muse G, Williams L, Burkholder A . Widespread transcriptional pausing and elongation control at enhancers. Genes Dev. 2018; 32(1):26-41. PMC: 5828392. DOI: 10.1101/gad.309351.117. View

18.

Davidson L, Francis L, Cordiner R, Eaton J, Estell C, Macias S . Rapid Depletion of DIS3, EXOSC10, or XRN2 Reveals the Immediate Impact of Exoribonucleolysis on Nuclear RNA Metabolism and Transcriptional Control. Cell Rep. 2019; 26(10):2779-2791.e5. PMC: 6403362. DOI: 10.1016/j.celrep.2019.02.012. View

19.

Tudek A, Schmid M, Makaras M, Barrass J, Beggs J, Jensen T . A Nuclear Export Block Triggers the Decay of Newly Synthesized Polyadenylated RNA. Cell Rep. 2018; 24(9):2457-2467.e7. PMC: 6130047. DOI: 10.1016/j.celrep.2018.07.103. View

20.

Fish L, Navickas A, Culbertson B, Xu Y, Nguyen H, Zhang S . Nuclear TARBP2 Drives Oncogenic Dysregulation of RNA Splicing and Decay. Mol Cell. 2019; 75(5):967-981.e9. PMC: 6731133. DOI: 10.1016/j.molcel.2019.06.001. View