Dynamic RNA 3′ Uridylation and Guanylation during Mitosis

Liu, Yusheng; Nie, Hu; Lu, Falong

doi:10.1016/j.isci.2020.101402

Cited by 8 publications

(7 citation statements)

References 24 publications

(35 reference statements)

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“…In addition, global translation efficiency varies a lot during different stages of mitotic cell cycle, while the poly(A) tail length changed only moderately for a small proportion of genes 23 . However, we noticed extensive changes in non-A residues during somatic cell cycle 32 . Since poly(A) tail length does not contribute to translational regulation in somatic cells as seen in reproductive cells, we asked whether the non-A residues, the base composition of poly(A) tails, affect the translation efficiency.…”

Section: Non-a Residues Are Associated With High Translation Efficiency In Vivomentioning

confidence: 84%

Enhancement of synthetic mRNA translation efficiency through engineered poly(A) tails

Liu

Nie

Sun

et al. 2021

Preprint

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In vitro transcribed (IVT) mRNA represents a new class of drug in both therapeutics and vaccines. Improving the translation efficiency of IVT mRNA remains a core challenge for mRNA-based applications. Here, using IVT mRNAs with poly(A) tails containing non-A residues which were recently revealed to be widespread in RNA poly(A) tails, we unexpectedly find that non-A residues can effectively promote the mRNA translation. To further support our finding, we provide evidence that non-A residues associated with enhanced mRNA translation efficiency transcriptome-wide in mouse and human cells. Together, our study provides a novel approach to enhance mRNA translation efficiency by inclusion of non-A residues in the mRNA poly(A) tails, holding great potential to promote mRNA-based therapeutics and vaccines.

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Section: Non-a Residues Are Associated With High Translation Efficiency In Vivomentioning

confidence: 84%

Enhancement of synthetic mRNA translation efficiency through engineered poly(A) tails

Liu

Nie

Sun

et al. 2021

Preprint

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“…The RNA metabolism wave is associated with the cell cycle 23 . In addition, the average/median mRNA half-life is known to be associated with cell cycle duration.…”

Section: Resultsmentioning

confidence: 99%

Degradation intermediates as an indicator of mRNA and cell metabolism

Liu

Zhang

Nie

et al. 2021

Preprint

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Traditional mRNA degradation rate measurements involves complex experimental design with RNA labeling or transcription blocking together with sampling at multiple timepoints. These experimental requirements limit the application of transcriptome-wide mRNA degradation rate analysis mainly in cultured cells, but rarely in in vivo samples. Therefore, a direct and simple strategy needs to be developed to study mRNA degradation rate. Here, we defined mRNA degradation intermediates as transcripts where decay is about to occur or has partially occurred in the 3′-untranslated regions after poly(A) tail deadenylation, and found that the proportion of mRNA degradation intermediates is a very simple and convenient indicator for evaluating the degradation rate of mRNA in mouse and human cell lines. In addition, we showed that a higher proportion of mRNA degradation intermediates is correlated with faster cell cycle and higher turnover rate of mouse tissues. Further, we validated that in mouse maturing oocytes where transcription is silent, the proportion of mRNA degradation intermediates is positively correlated with the mRNA degradation rate. Together, these results demonstrate that degradation intermediates can function as a good indicator of mRNA, cell, and tissue metabolism, and can be easily assayed by total RNA 3′-end sequencing from a single bulk cell sample without the need for drug treatment or multi-timepoint sampling. This finding is of great potential for studies on mRNA degradation rate at the molecular, cellular, or organic level, including samples or systems that cannot be assayed with previous methods. In addition, further application of the findings into single cells will likely greatly aid the identification and study of rare cells with unique cellular metabolism dynamics such as tissue stem cells and tumor cells.

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“…This process tends to be a key factor in germline development, differentiation, and early embryogenesis, where short-lived transcripts, with relatively fast turnover, predominate [ 33 ]. The lengths of poly(A) tails might also depend on circadian rhythms and the cell cycle [ 34 , 35 , 36 ]. By studying multiple mouse liver mRNAs, researchers demonstrated that rhythmic changes in poly(A) tail lengths were under the control of the circadian clock.…”

Section: Polyadenylation In Animal Cellsmentioning

confidence: 99%

“…With regard to the cell cycle, TAIL-Seq analysis suggests that global RNA decay takes place during the S phase through the accumulation of terminal uridylation. On the other hand, the accumulation of terminal guanylation occurs during the M phase of the cell cycle, leading to the assumption that the majority of the transcriptome is then protected from active deadenylation [ 35 ].…”

Section: Polyadenylation In Animal Cellsmentioning

confidence: 99%

Implications of Poly(A) Tail Processing in Repeat Expansion Diseases

Joachimiak

Ciesiolka

Figura

et al. 2022

Cells

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Repeat expansion diseases are a group of more than 40 disorders that affect mainly the nervous and/or muscular system and include myotonic dystrophies, Huntington’s disease, and fragile X syndrome. The mutation-driven expanded repeat tract occurs in specific genes and is composed of tri- to dodeca-nucleotide-long units. Mutant mRNA is a pathogenic factor or important contributor to the disease and has great potential as a therapeutic target. Although repeat expansion diseases are quite well known, there are limited studies concerning polyadenylation events for implicated transcripts that could have profound effects on transcript stability, localization, and translation efficiency. In this review, we briefly present polyadenylation and alternative polyadenylation (APA) mechanisms and discuss their role in the pathogenesis of selected diseases. We also discuss several methods for poly(A) tail measurement (both transcript-specific and transcriptome-wide analyses) and APA site identification—the further development and use of which may contribute to a better understanding of the correlation between APA events and repeat expansion diseases. Finally, we point out some future perspectives on the research into repeat expansion diseases, as well as APA studies.

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Dynamic RNA 3′ Uridylation and Guanylation during Mitosis

Cited by 8 publications

References 24 publications

Enhancement of synthetic mRNA translation efficiency through engineered poly(A) tails

Enhancement of synthetic mRNA translation efficiency through engineered poly(A) tails

Degradation intermediates as an indicator of mRNA and cell metabolism

Implications of Poly(A) Tail Processing in Repeat Expansion Diseases

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