Poly(A)-binding Protein Modulates MRNA Susceptibility to Cap-dependent MiRNA-mediated Repression

Overview

Journal RNA

Specialty Molecular Biology

Date 2009 Nov 26

PMID 19934229

Citations 41

Authors

Robert W Walters

Shelton S Bradrick

Matthias Gromeier

Affiliations

Soon will be listed here.

Abstract

MicroRNAs (miRNAs) regulate gene expression post-transcriptionally through binding specific sites within the 3' untranslated regions (UTRs) of their target mRNAs. Numerous investigations have documented repressive effects of miRNAs and identified factors required for their activity. However, the precise mechanisms by which miRNAs modulate gene expression are still obscure. Here, we have examined the effects of multiple miRNAs on diverse target transcripts containing artificial or naturally occurring 3' UTRs in human cell culture. In agreement with previous studies, we report that both the 5' m(7)G cap and 3' poly(A) tail are essential for maximum miRNA repression. These cis-acting elements also conferred miRNA susceptibility to target mRNAs translating under the control of viral- and eukaryotic mRNA-derived 5' UTR structures that enable cap-independent translation. Additionally, we evaluated a role for the poly(A)-binding protein (PABP) in miRNA function utilizing multiple approaches to modulate levels of active PABP in cells. PABP expression and activity inversely correlated with the strength of miRNA silencing, in part due to antagonism of target mRNA deadenylation. Together, these findings further define the cis- and trans-acting factors that modulate miRNA efficacy.

Citing Articles

Role of ROCK signaling in virus replication.

Kumar R, Barua S, Tripathi B, Kumar N Virus Res. 2023; 329:199105.

PMID: 36977446 PMC: 10194102. DOI: 10.1016/j.virusres.2023.199105.

Suppression of microRNA168 enhances salt tolerance in rice (Oryza sativa L.).

Wan J, Meng S, Wang Q, Zhao J, Qiu X, Wang L BMC Plant Biol. 2022; 22(1):563.

PMID: 36460977 PMC: 9719116. DOI: 10.1186/s12870-022-03959-1.

ROCK1/MLC2 inhibition induces decay of viral mRNA in BPXV infected cells.

Kumar R, Chander Y, Khandelwal N, Verma A, Rawat K, Shringi B Sci Rep. 2022; 12(1):17811.

PMID: 36280692 PMC: 9592580. DOI: 10.1038/s41598-022-21610-9.

Enhancing the yield of seasonal influenza viruses through manipulation of microRNAs in Madin-Darby canine kidney cells.

Saengchoowong S, Nimsamer P, Khongnomnan K, Poomipak W, Praianantathavorn K, Rattanaburi S Exp Biol Med (Maywood). 2022; 247(15):1335-1349.

PMID: 35666095 PMC: 9442458. DOI: 10.1177/15353702221098340.

Human La binds mRNAs through contacts to the poly(A) tail.

Vinayak J, Marrella S, Hussain R, Rozenfeld L, Solomon K, Bayfield M Nucleic Acids Res. 2018; 46(8):4228-4240.

PMID: 29447394 PMC: 5934636. DOI: 10.1093/nar/gky090.

References

Voeltz G, Ongkasuwan J, Standart N, Steitz J . A novel embryonic poly(A) binding protein, ePAB, regulates mRNA deadenylation in Xenopus egg extracts. Genes Dev. 2001; 15(6):774-88. PMC: 312653. DOI: 10.1101/gad.872201. View

Zeng Y, Yi R, Cullen B . MicroRNAs and small interfering RNAs can inhibit mRNA expression by similar mechanisms. Proc Natl Acad Sci U S A. 2003; 100(17):9779-84. PMC: 187842. DOI: 10.1073/pnas.1630797100. View

Martineau Y, Derry M, Wang X, Yanagiya A, Berlanga J, Shyu A . Poly(A)-binding protein-interacting protein 1 binds to eukaryotic translation initiation factor 3 to stimulate translation. Mol Cell Biol. 2008; 28(21):6658-67. PMC: 2573229. DOI: 10.1128/MCB.00738-08. View

Kaiser C, Dobrikova E, Bradrick S, Shveygert M, Herbert J, Gromeier M . Activation of cap-independent translation by variant eukaryotic initiation factor 4G in vivo. RNA. 2008; 14(10):2170-82. PMC: 2553731. DOI: 10.1261/rna.1171808. View

Olsen P, Ambros V . The lin-4 regulatory RNA controls developmental timing in Caenorhabditis elegans by blocking LIN-14 protein synthesis after the initiation of translation. Dev Biol. 2000; 216(2):671-80. DOI: 10.1006/dbio.1999.9523. View

Gottwein E, Mukherjee N, Sachse C, Frenzel C, Majoros W, Chi J . A viral microRNA functions as an orthologue of cellular miR-155. Nature. 2007; 450(7172):1096-9. PMC: 2614920. DOI: 10.1038/nature05992. View

Kiriakidou M, Tan G, Lamprinaki S, de Planell-Saguer M, Nelson P, Mourelatos Z . An mRNA m7G cap binding-like motif within human Ago2 represses translation. Cell. 2007; 129(6):1141-51. DOI: 10.1016/j.cell.2007.05.016. View

Thermann R, Hentze M . Drosophila miR2 induces pseudo-polysomes and inhibits translation initiation. Nature. 2007; 447(7146):875-8. DOI: 10.1038/nature05878. View

Craig A, Haghighat A, Yu A, Sonenberg N . Interaction of polyadenylate-binding protein with the eIF4G homologue PAIP enhances translation. Nature. 1998; 392(6675):520-3. DOI: 10.1038/33198. View

10.

Bagga S, Bracht J, Hunter S, Massirer K, Holtz J, Eachus R . Regulation by let-7 and lin-4 miRNAs results in target mRNA degradation. Cell. 2005; 122(4):553-63. DOI: 10.1016/j.cell.2005.07.031. View

11.

Weinmann L, Hock J, Ivacevic T, Ohrt T, Mutze J, Schwille P . Importin 8 is a gene silencing factor that targets argonaute proteins to distinct mRNAs. Cell. 2009; 136(3):496-507. DOI: 10.1016/j.cell.2008.12.023. View

12.

Zeng Y, Cullen B . Sequence requirements for micro RNA processing and function in human cells. RNA. 2003; 9(1):112-23. PMC: 1370375. DOI: 10.1261/rna.2780503. View

13.

Kim V, Nam J . Genomics of microRNA. Trends Genet. 2006; 22(3):165-73. DOI: 10.1016/j.tig.2006.01.003. View

14.

Eulalio A, Huntzinger E, Izaurralde E . GW182 interaction with Argonaute is essential for miRNA-mediated translational repression and mRNA decay. Nat Struct Mol Biol. 2008; 15(4):346-53. DOI: 10.1038/nsmb.1405. View

15.

Katoh T, Sakaguchi Y, Miyauchi K, Suzuki T, Kashiwabara S, Baba T . Selective stabilization of mammalian microRNAs by 3' adenylation mediated by the cytoplasmic poly(A) polymerase GLD-2. Genes Dev. 2009; 23(4):433-8. PMC: 2648654. DOI: 10.1101/gad.1761509. View

16.

Barreau C, Dutertre S, Paillard L, Osborne H . Liposome-mediated RNA transfection should be used with caution. RNA. 2006; 12(10):1790-3. PMC: 1581979. DOI: 10.1261/rna.191706. View

17.

Wang B, Love T, Call M, Doench J, Novina C . Recapitulation of short RNA-directed translational gene silencing in vitro. Mol Cell. 2006; 22(4):553-60. DOI: 10.1016/j.molcel.2006.03.034. View

18.

Hundsdoerfer P, Thoma C, Hentze M . Eukaryotic translation initiation factor 4GI and p97 promote cellular internal ribosome entry sequence-driven translation. Proc Natl Acad Sci U S A. 2005; 102(38):13421-6. PMC: 1224658. DOI: 10.1073/pnas.0506536102. View

19.

Bradrick S, Dobrikova E, Kaiser C, Shveygert M, Gromeier M . Poly(A)-binding protein is differentially required for translation mediated by viral internal ribosome entry sites. RNA. 2007; 13(9):1582-93. PMC: 1950770. DOI: 10.1261/rna.556107. View

20.

Lowe B, Avila H, Bloom F, Gleeson M, Kusser W . Quantitation of gene expression in neural precursors by reverse-transcription polymerase chain reaction using self-quenched, fluorogenic primers. Anal Biochem. 2003; 315(1):95-105. DOI: 10.1016/s0003-2697(02)00695-4. View