Splicing Enhances Translation in Mammalian Cells: an Additional Function of the Exon Junction Complex

Overview

Journal Genes Dev

Specialty Molecular Biology

Date 2004 Jan 31

PMID 14752011

Citations 206

Authors

Ajit Nott

Herve Le Hir

Melissa J Moore

Affiliations

Soon will be listed here.

Abstract

In mammalian cells, spliced mRNAs yield greater quantities of protein per mRNA molecule than do otherwise identical mRNAs not made by splicing. This increased translational yield correlates with enhanced cytoplasmic polysome association of spliced mRNAs, and is attributable to deposition of exon junction complexes (EJCs). Translational stimulation can be replicated by tethering the EJC proteins Y14, Magoh, and RNPS1 or the nonsense-mediated decay (NMD) factors Upf1, Upf2, and Upf3b to an intronless reporter mRNA. Thus, in addition to its previously characterized role in NMD, the EJC also promotes mRNA polysome association. Furthermore, the ability to stimulate translation when bound inside an open reading frame appears to be a general feature of factors required for NMD.

Citing Articles

Long-term safety of lentiviral or gammaretroviral gene-modified T cell therapies.

Jadlowsky J, Hexner E, Marshall A, Grupp S, Frey N, Riley J Nat Med. 2025; .

PMID: 39833408 DOI: 10.1038/s41591-024-03478-6.

Translation of circular RNAs.

Margvelani G, Maquera K, Welden J, Rodgers D, Stamm S Nucleic Acids Res. 2024; 53(1.

PMID: 39660652 PMC: 11724312. DOI: 10.1093/nar/gkae1167.

Widespread regulation of the maternal transcriptome by Nanos in Drosophila.

Marhabaie M, Wharton T, Kim S, Wharton R PLoS Biol. 2024; 22(10):e3002840.

PMID: 39401257 PMC: 11501031. DOI: 10.1371/journal.pbio.3002840.

Current limitations in predicting mRNA translation with deep learning models.

Schlusser N, Gonzalez A, Pandey M, Zavolan M Genome Biol. 2024; 25(1):227.

PMID: 39164757 PMC: 11337900. DOI: 10.1186/s13059-024-03369-6.

Study of the RNA splicing kinetics via in vivo 5-EU labeling.

Bolikhova A, Buyan A, Mariasina S, Rudenko A, Chekh D, Mazur A RNA. 2024; 30(10):1356-1373.

PMID: 39048310 PMC: 11404452. DOI: 10.1261/rna.079937.123.

References

Mendell J, Medghalchi S, Lake R, Noensie E, Dietz H . Novel Upf2p orthologues suggest a functional link between translation initiation and nonsense surveillance complexes. Mol Cell Biol. 2000; 20(23):8944-57. PMC: 86549. DOI: 10.1128/MCB.20.23.8944-8957.2000. View

Le Hir H, Izaurralde E, Maquat L, Moore M . The spliceosome deposits multiple proteins 20-24 nucleotides upstream of mRNA exon-exon junctions. EMBO J. 2000; 19(24):6860-9. PMC: 305905. DOI: 10.1093/emboj/19.24.6860. View

Shu M, Steitz J . Human Upf proteins target an mRNA for nonsense-mediated decay when bound downstream of a termination codon. Cell. 2001; 103(7):1121-31. DOI: 10.1016/s0092-8674(00)00214-2. View

Wang W, Czaplinski K, Rao Y, Peltz S . The role of Upf proteins in modulating the translation read-through of nonsense-containing transcripts. EMBO J. 2001; 20(4):880-90. PMC: 145432. DOI: 10.1093/emboj/20.4.880. View

Schwer B . A new twist on RNA helicases: DExH/D box proteins as RNPases. Nat Struct Biol. 2001; 8(2):113-6. DOI: 10.1038/84091. View

Maquat L, Carmichael G . Quality control of mRNA function. Cell. 2001; 104(2):173-6. DOI: 10.1016/s0092-8674(01)00202-1. View

He F, Jacobson A . Upf1p, Nmd2p, and Upf3p regulate the decapping and exonucleolytic degradation of both nonsense-containing mRNAs and wild-type mRNAs. Mol Cell Biol. 2001; 21(5):1515-30. PMC: 86698. DOI: 10.1128/MCB.21.5.1515-1530.2001. View

Will C, Luhrmann R . Molecular biology. RNP remodeling with DExH/D boxes. Science. 2001; 291(5510):1916-7. DOI: 10.1126/science.1059682. View

McKendrick L, Thompson E, Ferreira J, Morley S, Lewis J . Interaction of eukaryotic translation initiation factor 4G with the nuclear cap-binding complex provides a link between nuclear and cytoplasmic functions of the m(7) guanosine cap. Mol Cell Biol. 2001; 21(11):3632-41. PMC: 86986. DOI: 10.1128/MCB.21.11.3632-3641.2001. View

10.

Mendez R, Richter J . Translational control by CPEB: a means to the end. Nat Rev Mol Cell Biol. 2001; 2(7):521-9. DOI: 10.1038/35080081. View

11.

Le Hir H, Gatfield D, Izaurralde E, Moore M . The exon-exon junction complex provides a binding platform for factors involved in mRNA export and nonsense-mediated mRNA decay. EMBO J. 2001; 20(17):4987-97. PMC: 125616. DOI: 10.1093/emboj/20.17.4987. View

12.

Kim V, Kataoka N, Dreyfuss G . Role of the nonsense-mediated decay factor hUpf3 in the splicing-dependent exon-exon junction complex. Science. 2001; 293(5536):1832-6. DOI: 10.1126/science.1062829. View

13.

Shu M, Steitz J . Communication of the position of exon-exon junctions to the mRNA surveillance machinery by the protein RNPS1. Science. 2001; 293(5536):1836-9. DOI: 10.1126/science.1062786. View

14.

Luo M, Zhou Z, Magni K, Christoforides C, Rappsilber J, Mann M . Pre-mRNA splicing and mRNA export linked by direct interactions between UAP56 and Aly. Nature. 2001; 413(6856):644-7. DOI: 10.1038/35098106. View

15.

Wilusz C, Wang W, Peltz S . Curbing the nonsense: the activation and regulation of mRNA surveillance. Genes Dev. 2001; 15(21):2781-5. DOI: 10.1101/gad.943701. View

16.

Mohr S, Dillon S, BOSWELL R . The RNA-binding protein Tsunagi interacts with Mago Nashi to establish polarity and localize oskar mRNA during Drosophila oogenesis. Genes Dev. 2001; 15(21):2886-99. PMC: 312802. DOI: 10.1101/gad.927001. View

17.

Hachet O, Ephrussi A . Drosophila Y14 shuttles to the posterior of the oocyte and is required for oskar mRNA transport. Curr Biol. 2001; 11(21):1666-74. DOI: 10.1016/s0960-9822(01)00508-5. View

18.

Gatfield D, Le Hir H, Schmitt C, Braun I, Kocher T, Wilm M . The DExH/D box protein HEL/UAP56 is essential for mRNA nuclear export in Drosophila. Curr Biol. 2001; 11(21):1716-21. DOI: 10.1016/s0960-9822(01)00532-2. View

19.

Kataoka N, Diem M, Kim V, Yong J, Dreyfuss G . Magoh, a human homolog of Drosophila mago nashi protein, is a component of the splicing-dependent exon-exon junction complex. EMBO J. 2001; 20(22):6424-33. PMC: 125744. DOI: 10.1093/emboj/20.22.6424. View

20.

McCracken S, Lambermon M, Blencowe B . SRm160 splicing coactivator promotes transcript 3'-end cleavage. Mol Cell Biol. 2001; 22(1):148-60. PMC: 134228. DOI: 10.1128/MCB.22.1.148-160.2002. View