General RNA Binding Proteins Render Translation Cap Dependent

Overview

Journal EMBO J

Specialties Biotechnology
Molecular Biology

Date 1996 Dec 16

PMID 9003790

Citations 86

Authors

Y V Svitkin

L P Ovchinnikov

G Dreyfuss

N Sonenberg

Affiliations

Soon will be listed here.

Abstract

Translation in rabbit reticulocyte lysate is relatively independent of the presence of the mRNA m7G cap structure and the cap binding protein, eIF-4E. In addition, initiation occurs frequently at spurious internal sites. Here we show that a critical parameter which contributes to cap-dependent translation is the amount of general RNA binding proteins in the extract. Addition of several general RNA binding proteins, such as hnRNP A1, La autoantigen, pyrimidine tract binding protein (hnRNP I/PTB) and the major core protein of cytoplasmic mRNP (p50), rendered translation in a rabbit reticulocyte lysate cap dependent. These proteins drastically inhibited the translation of an uncapped mRNA, but had no effect on translation of a capped mRNA. Based on these and other results, we suggest that one function of general mRNA binding proteins in the cytoplasm is to promote ribosome binding by a 5' end, cap-mediated mechanism, and prevent spurious initiations at aberrant translation start sites.

Citing Articles

Optimizing Human Cell-Free System for Efficient Protein Production.

Mansour A, Kipper K, Pulk A J Microbiol Biotechnol. 2025; 35:e2410026.

PMID: 40016147 PMC: 11896798. DOI: 10.4014/jmb.2410.10026.

Biological functions of 5-methylcytosine RNA-binding proteins and their potential mechanisms in human cancers.

Zhao T, Zhang Z, Chen Z, Xu G, Wang Y, Wang F Front Oncol. 2025; 15:1534948.

PMID: 39990690 PMC: 11842269. DOI: 10.3389/fonc.2025.1534948.

Insights into the Mode and Mechanism of Interactions Between RNA and RNA-Binding Proteins.

Fang Y, Liu X, Liu Y, Xu N Int J Mol Sci. 2024; 25(21).

PMID: 39518890 PMC: 11545484. DOI: 10.3390/ijms252111337.

Classification, replication, and transcription of .

Liao Y, Wang H, Liao H, Sun Y, Tan L, Song C Front Microbiol. 2024; 14:1291761.

PMID: 38328580 PMC: 10847374. DOI: 10.3389/fmicb.2023.1291761.

The flavagline FL3 interferes with the association of Annexin A2 with the eIF4F initiation complex and transiently stimulates the translation of A2 mRNA.

Grindheim A, Patil S, Nebigil C, Desaubry L, Vedeler A Front Cell Dev Biol. 2023; 11:1094941.

PMID: 37250892 PMC: 10214161. DOI: 10.3389/fcell.2023.1094941.

References

Bachmann M, Falke D, Schroder H, Muller W . Intracellular distribution of the La antigen in CV-1 cells after herpes simplex virus type 1 infection compared with the localization of U small nuclear ribonucleoprotein particles. J Gen Virol. 1989; 70 ( Pt 4):881-91. DOI: 10.1099/0022-1317-70-4-881. View

Stefano J . Purified lupus antigen La recognizes an oligouridylate stretch common to the 3' termini of RNA polymerase III transcripts. Cell. 1984; 36(1):145-54. DOI: 10.1016/0092-8674(84)90083-7. View

de Smit M, van Duin J . Control of prokaryotic translational initiation by mRNA secondary structure. Prog Nucleic Acid Res Mol Biol. 1990; 38:1-35. DOI: 10.1016/s0079-6603(08)60707-2. View

Kozak M . Evaluation of the fidelity of initiation of translation in reticulocyte lysates from commercial sources. Nucleic Acids Res. 1990; 18(9):2828. PMC: 330786. DOI: 10.1093/nar/18.9.2828. View

Adhin M, van Duin J . Scanning model for translational reinitiation in eubacteria. J Mol Biol. 1990; 213(4):811-8. DOI: 10.1016/S0022-2836(05)80265-7. View

Boni I, Isaeva D, Musychenko M, Tzareva N . Ribosome-messenger recognition: mRNA target sites for ribosomal protein S1. Nucleic Acids Res. 1991; 19(1):155-62. PMC: 333546. DOI: 10.1093/nar/19.1.155. View

Frederickson R, Montine K, Sonenberg N . Phosphorylation of eukaryotic translation initiation factor 4E is increased in Src-transformed cell lines. Mol Cell Biol. 1991; 11(5):2896-900. PMC: 360080. DOI: 10.1128/mcb.11.5.2896-2900.1991. View

Anthony D, Merrick W . Eukaryotic initiation factor (eIF)-4F. Implications for a role in internal initiation of translation. J Biol Chem. 1991; 266(16):10218-26. View

Pestova T, Hellen C, Wimmer E . Translation of poliovirus RNA: role of an essential cis-acting oligopyrimidine element within the 5' nontranslated region and involvement of a cellular 57-kilodalton protein. J Virol. 1991; 65(11):6194-204. PMC: 250311. DOI: 10.1128/JVI.65.11.6194-6204.1991. View

10.

Hambidge S, Sarnow P . Terminal 7-methyl-guanosine cap structure on the normally uncapped 5' noncoding region of poliovirus mRNA inhibits its translation in mammalian cells. J Virol. 1991; 65(11):6312-5. PMC: 250341. DOI: 10.1128/JVI.65.11.6312-6315.1991. View

11.

Mayeda A, Krainer A . Regulation of alternative pre-mRNA splicing by hnRNP A1 and splicing factor SF2. Cell. 1992; 68(2):365-75. DOI: 10.1016/0092-8674(92)90477-t. View

12.

Scheper G, VOORMA H, Thomas A . Eukaryotic initiation factors-4E and -4F stimulate 5' cap-dependent as well as internal initiation of protein synthesis. J Biol Chem. 1992; 267(11):7269-74. View

13.

Ghetti A, Pinol-Roma S, Michael W, Morandi C, Dreyfuss G . hnRNP I, the polypyrimidine tract-binding protein: distinct nuclear localization and association with hnRNAs. Nucleic Acids Res. 1992; 20(14):3671-8. PMC: 334017. DOI: 10.1093/nar/20.14.3671. View

14.

Meerovitch K, Svitkin Y, Lee H, Lejbkowicz F, Kenan D, Chan E . La autoantigen enhances and corrects aberrant translation of poliovirus RNA in reticulocyte lysate. J Virol. 1993; 67(7):3798-807. PMC: 237744. DOI: 10.1128/JVI.67.7.3798-3807.1993. View

15.

Dreyfuss G, Matunis M, Pinol-Roma S, Burd C . hnRNP proteins and the biogenesis of mRNA. Annu Rev Biochem. 1993; 62:289-321. DOI: 10.1146/annurev.bi.62.070193.001445. View

16.

Portman D, Dreyfuss G . RNA annealing activities in HeLa nuclei. EMBO J. 1994; 13(1):213-21. PMC: 394795. DOI: 10.1002/j.1460-2075.1994.tb06251.x. View

17.

Svitkin Y, Meerovitch K, Lee H, Dholakia J, Kenan D, Agol V . Internal translation initiation on poliovirus RNA: further characterization of La function in poliovirus translation in vitro. J Virol. 1994; 68(3):1544-50. PMC: 236611. DOI: 10.1128/JVI.68.3.1544-1550.1994. View

18.

Pause A, Methot N, Svitkin Y, Merrick W, Sonenberg N . Dominant negative mutants of mammalian translation initiation factor eIF-4A define a critical role for eIF-4F in cap-dependent and cap-independent initiation of translation. EMBO J. 1994; 13(5):1205-15. PMC: 394930. DOI: 10.1002/j.1460-2075.1994.tb06370.x. View

19.

Witherell G, Wimmer E . Encephalomyocarditis virus internal ribosomal entry site RNA-protein interactions. J Virol. 1994; 68(5):3183-92. PMC: 236809. DOI: 10.1128/JVI.68.5.3183-3192.1994. View

20.

Sonenberg N . Remarks on the mechanism of ribosome binding to eukaryotic mRNAs. Gene Expr. 1993; 3(3):317-23. PMC: 6081619. View