Crosstalk between alternative polyadenylation and miRNAs in the regulation of protein translational efficiency
- Yonggui Fu1,3,
- Liutao Chen1,3,
- Chengyong Chen1,
- Yutong Ge1,
- Mingjing Kang1,
- Zili Song1,
- Jingwen Li1,
- Yuchao Feng1,
- Zhanfeng Huo1,
- Guopei He1,
- Mengmeng Hou1,
- Shangwu Chen1 and
- Anlong Xu1,2
- 1State Key Laboratory for Biocontrol, Guangdong Province Key Laboratory of Pharmaceutical Functional Genes, Department of Biochemistry, School of Life Sciences, Sun Yat-sen University, Higher Education Mega Center, Guangzhou, 510006, China;
- 2School of Life Sciences, Beijing University of Chinese Medicine, Beijing, 100029, China
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↵3 These authors contributed equally to this work.
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.
Footnotes
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[Supplemental material is available for this article.]
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Article published online before print. Article, supplemental material, and publication date are at http://www.genome.org/cgi/doi/10.1101/gr.231506.117.
- Received October 24, 2017.
- Accepted September 11, 2018.
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