Crosstalk between alternative polyadenylation and miRNAs in the regulation of protein translational efficiency

Fu, Yonggui; Chen, Liutao; Chen, Chengyong; Ge, Yutong; Kang, Mingjing; Song, Zili; Li, Jingwen; Feng, Yuchao; Huo, Zhanfeng; He, Guopei; Hou, Mingxiao; Chen, Shangwu; Xu, Anlong

doi:10.1101/gr.231506.117

Cited by 40 publications

(33 citation statements)

References 35 publications

(51 reference statements)

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“…In fact, a recent study has reported that in some cell lines, distal PAS usage resulting in lengthened 3′UTR decreases polysome occupancy and represses mRNA translation in comparison with shortened 3′UTR isoform. 108 Therefore, the impact of 3′UTR APA on mRNA translation may vary in a gene- and 3′UTR sequence-dependent manner. Further work is required to delineate how various cis elements affect the translation efficiency of APA isoforms in different conditions and different cell types.…”

Section: Molecular Effects Of Apamentioning

confidence: 99%

Alternative polyadenylation of mRNA and its role in cancer

et al. 2021

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Alternative polyadenylation (APA) is a molecular process that generates diversity at the 3′ end of RNA polymerase II transcripts from over 60% of human genes. APA is derived from the existence of multiple polyadenylation signals (PAS) within the same transcript, and results in the differential inclusion of sequence information at the 3′ end. While APA can occur between two PASs allowing for generation of transcripts with distinct coding potential from a single gene, most APA occurs within the untranslated region (3′UTR) and changes the length and content of these non-coding sequences. APA within the 3′UTR can have tremendous impact on its regulatory potential of the mRNA through a variety of mechanisms, and indeed this layer of gene expression regulation has profound impact on processes vital to cell growth and development. Recent studies have particularly highlighted the importance of APA dysregulation in cancer onset and progression. Here, we review the current knowledge of APA and its impacts on mRNA stability, translation, localization and protein localization. We also discuss the implications of APA dysregulation in cancer research and therapy.

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Section: Molecular Effects Of Apamentioning

confidence: 99%

Alternative polyadenylation of mRNA and its role in cancer

et al. 2021

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“…In contrast to ribosome profiling, which determines the position of ribosomes within mRNA coding sequence, polysome profiling enables the analysis of entire mRNA transcripts. Consequently, this permits the study of individual transcript isoforms with particular resonance for the identification of conserved cis-acting sequences and structural motifs that can participate in transcript-specific translational regulation [18][19][20][21]. Furthermore, polysome profiling is readily combinable with several downstream applications, including microarrays and next generation sequencing (NGS) techniques, to identify polysome-bound mRNAs [16,20,21].…”

Section: Introductionmentioning

confidence: 99%

Identifying the Translatome of Mouse NEBD-Stage Oocytes via SSP-Profiling; A Novel Polysome Fractionation Method

Mašek

Llano

Gahurová

et al. 2020

IJMS

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Meiotic maturation of oocyte relies on pre-synthesised maternal mRNA, the translation of which is highly coordinated in space and time. Here, we provide a detailed polysome profiling protocol that demonstrates a combination of the sucrose gradient ultracentrifugation in small SW55Ti tubes with the qRT-PCR-based quantification of 18S and 28S rRNAs in fractionated polysome profile. This newly optimised method, named Scarce Sample Polysome Profiling (SSP-profiling), is suitable for both scarce and conventional sample sizes and is compatible with downstream RNA-seq to identify polysome associated transcripts. Utilising SSP-profiling we have assayed the translatome of mouse oocytes at the onset of nuclear envelope breakdown (NEBD)—a developmental point, the study of which is important for furthering our understanding of the molecular mechanisms leading to oocyte aneuploidy. Our analyses identified 1847 transcripts with moderate to strong polysome occupancy, including abundantly represented mRNAs encoding mitochondrial and ribosomal proteins, proteasomal components, glycolytic and amino acids synthetic enzymes, proteins involved in cytoskeleton organization plus RNA-binding and translation initiation factors. In addition to transcripts encoding known players of meiotic progression, we also identified several mRNAs encoding proteins of unknown function. Polysome profiles generated using SSP-profiling were more than comparable to those developed using existing conventional approaches, being demonstrably superior in their resolution, reproducibility, versatility, speed of derivation and downstream protocol applicability.

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“…Curiously, VSV infection has also been reported to cause widespread shortening of host mRNA 3′UTR via alternative polyadenylation (X. Jia et al, 2017). The shortening events occurred more frequently in genes functioning in antiviral and interferon signaling suggest that such 3′UTR shortening is an integrated antiviral response, potentially to enhance the translation efficiency of the antiviral mRNAs via removal of miRNA‐binding site (Y. Fu et al, 2018; Mayr & Bartel, 2009). Our group has also reported that virus infection causes an alternative 5′UTR event that enhances the translation of the ciliopathy gene INPP5E, the expression of which inhibits HSV and VSV infection (Hoang et al, 2019).…”

Section: Emerging Translation Strategies During Virus–host Interactionmentioning

confidence: 99%

Emerging translation strategies during virus–host interaction

et al. 2020

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Translation control is crucial during virus–host interaction. On one hand, viruses completely rely on the protein synthesis machinery of host cells to propagate and have evolved various mechanisms to redirect the host's ribosomes toward their viral mRNAs. On the other hand, the host rewires its translation program in an attempt to contain and suppress the virus early on during infection; the antiviral program includes specific control on protein synthesis to translate several antiviral mRNAs involved in quenching the infection. As the infection progresses, host translation is in turn inhibited in order to limit viral propagation. We have learnt of very diverse strategies that both parties utilize to gain or retain control over the protein synthesis machinery. Yet novel strategies continue to be discovered, attesting for the importance of mRNA translation in virus–host interaction. This review focuses on recently described translation strategies employed by both hosts and viruses. These discoveries provide additional pieces in the understanding of the complex virus–host translation landscape. This article is categorized under: Translation > Translation Mechanisms Translation > Translation Regulation

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Crosstalk between alternative polyadenylation and miRNAs in the regulation of protein translational efficiency

Cited by 40 publications

References 35 publications

Alternative polyadenylation of mRNA and its role in cancer

Alternative polyadenylation of mRNA and its role in cancer

Identifying the Translatome of Mouse NEBD-Stage Oocytes via SSP-Profiling; A Novel Polysome Fractionation Method

Emerging translation strategies during virus–host interaction

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