Crosstalk Between Alternative Polyadenylation and MiRNAs in the Regulation of Protein Translational Efficiency

Overview

Journal Genome Res

Specialty Genetics

Date 2018 Sep 20

PMID 30228199

Citations 21

Authors

Yonggui Fu

Liutao Chen

Chengyong Chen

Yutong Ge

Mingjing Kang

Zili Song

Jingwen Li

Yuchao Feng

Zhanfeng Huo

Guopei He

Mengmeng Hou

Shangwu Chen

Anlong Xu

Affiliations

Soon will be listed here.

Abstract

3' UTRs play important roles in the gene regulation network via their influence on mRNA stability, translational efficiency, and subcellular localization. For a given gene, 3' UTRs of different lengths generated by alternative polyadenylation (APA) may result in functional differences in regulation. The mechanistic details of how length changes of 3' UTRs alter gene function remain unclear. By combining APA sequencing and polysome profiling, we observed that mRNA isoforms with shorter 3' UTRs were bound with more polysomes in six cell lines but not in NIH3T3 cells, suggesting that changing 3' UTRs to shorter isoforms may lead to a higher gene translational efficiency. By interfering with the expression of TNRC6A and analyzing AGO2-PAR-CLIP data, we revealed that the APA effect on translational efficiency was mainly regulated by miRNAs, and this regulation was cell cycle dependent. The discrepancy between NIH3T3 and other cell lines was due to contact inhibition of NIH3T3. Thus, the crosstalk between APA and miRNAs may be needed for the regulation of protein translational efficiency.

Citing Articles

Disruption of PABPN1 phase separation by SNRPD2 drives colorectal cancer cell proliferation and migration through promoting alternative polyadenylation of CTNNBIP1.

Hu Z, Li M, Chen Y, Chen L, Han Y, Chen C Sci China Life Sci. 2024; 67(6):1212-1225.

PMID: 38811444 DOI: 10.1007/s11427-023-2495-x.

Identification of cuproptosis-related miRNAs in triple-negative breast cancer and analysis of the miRNA-mRNA regulatory network.

Wang Y, Wang J, Jiang J, Zhang W, Sun L, Ge Q Heliyon. 2024; 10(7):e28242.

PMID: 38601669 PMC: 11004712. DOI: 10.1016/j.heliyon.2024.e28242.

Nudt21-mediated alternative polyadenylation of MZT1 3'UTR contributes to pancreatic cancer progression.

Zhou Y, Yang J, Huang L, Liu C, Yu M, Chen R iScience. 2024; 27(2):108822.

PMID: 38303721 PMC: 10831950. DOI: 10.1016/j.isci.2024.108822.

Microbiota affects mitochondria and immune cell infiltrations via alternative polyadenylation during postnatal heart development.

Liu X, Shao Y, Han L, Zhu Y, Tu J, Ma J Front Cell Dev Biol. 2024; 11:1310409.

PMID: 38283994 PMC: 10820713. DOI: 10.3389/fcell.2023.1310409.

Immune-response 3'UTR alternative polyadenylation quantitative trait loci contribute to variation in human complex traits and diseases.

Li L, Ma X, Cui Y, Rotival M, Chen W, Zou X Nat Commun. 2023; 14(1):8347.

PMID: 38102153 PMC: 10724249. DOI: 10.1038/s41467-023-44191-1.

References

Fu Y, Sun Y, Li Y, Li J, Rao X, Chen C . Differential genome-wide profiling of tandem 3' UTRs among human breast cancer and normal cells by high-throughput sequencing. Genome Res. 2011; 21(5):741-7. PMC: 3083091. DOI: 10.1101/gr.115295.110. View

Vasudevan S, Tong Y, Steitz J . Cell-cycle control of microRNA-mediated translation regulation. Cell Cycle. 2008; 7(11):1545-9. PMC: 2556257. DOI: 10.4161/cc.7.11.6018. View

Sandberg R, Neilson J, Sarma A, Sharp P, Burge C . Proliferating cells express mRNAs with shortened 3' untranslated regions and fewer microRNA target sites. Science. 2008; 320(5883):1643-7. PMC: 2587246. DOI: 10.1126/science.1155390. View

Li Y, Sun Y, Fu Y, Li M, Huang G, Zhang C . Dynamic landscape of tandem 3' UTRs during zebrafish development. Genome Res. 2012; 22(10):1899-906. PMC: 3460185. DOI: 10.1101/gr.128488.111. View

Hoffman Y, Bublik D, Ugalde A, Elkon R, Biniashvili T, Agami R . 3'UTR Shortening Potentiates MicroRNA-Based Repression of Pro-differentiation Genes in Proliferating Human Cells. PLoS Genet. 2016; 12(2):e1005879. PMC: 4764332. DOI: 10.1371/journal.pgen.1005879. View

Truesdell S, Mortensen R, Seo M, Schroeder J, Lee J, LeTonqueze O . MicroRNA-mediated mRNA translation activation in quiescent cells and oocytes involves recruitment of a nuclear microRNP. Sci Rep. 2012; 2:842. PMC: 3496365. DOI: 10.1038/srep00842. View

Gandin V, Sikstrom K, Alain T, Morita M, McLaughlan S, Larsson O . Polysome fractionation and analysis of mammalian translatomes on a genome-wide scale. J Vis Exp. 2014; (87). PMC: 4189431. DOI: 10.3791/51455. View

Spies N, Burge C, Bartel D . 3' UTR-isoform choice has limited influence on the stability and translational efficiency of most mRNAs in mouse fibroblasts. Genome Res. 2013; 23(12):2078-90. PMC: 3847777. DOI: 10.1101/gr.156919.113. View

Fu Y, Ge Y, Sun Y, Liang J, Wan L, Wu X . IVT-SAPAS: Low-Input and Rapid Method for Sequencing Alternative Polyadenylation Sites. PLoS One. 2015; 10(12):e0145477. PMC: 4692544. DOI: 10.1371/journal.pone.0145477. View

10.

Di Giammartino D, Nishida K, Manley J . Mechanisms and consequences of alternative polyadenylation. Mol Cell. 2011; 43(6):853-66. PMC: 3194005. DOI: 10.1016/j.molcel.2011.08.017. View

11.

Filipowicz W, Bhattacharyya S, Sonenberg N . Mechanisms of post-transcriptional regulation by microRNAs: are the answers in sight?. Nat Rev Genet. 2008; 9(2):102-14. DOI: 10.1038/nrg2290. View

12.

Jia X, Yuan S, Wang Y, Fu Y, Ge Y, Ge Y . The role of alternative polyadenylation in the antiviral innate immune response. Nat Commun. 2017; 8:14605. PMC: 5333124. DOI: 10.1038/ncomms14605. View

13.

Cao Q, de Moor C, Mendez R, Richter J . Maskin is a CPEB-associated factor that transiently interacts with elF-4E. Mol Cell. 2000; 4(6):1017-27. DOI: 10.1016/s1097-2765(00)80230-0. View

14.

Fabian M, Sonenberg N, Filipowicz W . Regulation of mRNA translation and stability by microRNAs. Annu Rev Biochem. 2010; 79:351-79. DOI: 10.1146/annurev-biochem-060308-103103. View

15.

Huntzinger E, Izaurralde E . Gene silencing by microRNAs: contributions of translational repression and mRNA decay. Nat Rev Genet. 2011; 12(2):99-110. DOI: 10.1038/nrg2936. View

16.

Wells S, Hillner P, Vale R, Sachs A . Circularization of mRNA by eukaryotic translation initiation factors. Mol Cell. 1998; 2(1):135-40. DOI: 10.1016/s1097-2765(00)80122-7. View

17.

Yang Z, Jakymiw A, Wood M, Eystathioy T, Rubin R, Fritzler M . GW182 is critical for the stability of GW bodies expressed during the cell cycle and cell proliferation. J Cell Sci. 2004; 117(Pt 23):5567-78. DOI: 10.1242/jcs.01477. View

18.

Lin Y, Li Z, Ozsolak F, Kim S, Arango-Argoty G, Liu T . An in-depth map of polyadenylation sites in cancer. Nucleic Acids Res. 2012; 40(17):8460-71. PMC: 3458571. DOI: 10.1093/nar/gks637. View

19.

Mayr C, Bartel D . Widespread shortening of 3'UTRs by alternative cleavage and polyadenylation activates oncogenes in cancer cells. Cell. 2009; 138(4):673-84. PMC: 2819821. DOI: 10.1016/j.cell.2009.06.016. View

20.

Vasudevan S, Steitz J . AU-rich-element-mediated upregulation of translation by FXR1 and Argonaute 2. Cell. 2007; 128(6):1105-18. PMC: 3430382. DOI: 10.1016/j.cell.2007.01.038. View