Screening by deep sequencing reveals mediators of microRNA tailing in<i>C. elegans</i>

Prothro, Katherine Perkins; Vieux, Karl-Frédéric; Palmer, Cameron D.; Veksler-Lublinsky, Isana; McJunkin, Katherine

doi:10.1101/2021.01.11.426275

Cited by 6 publications

(15 citation statements)

References 90 publications

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“…In embryos and L1s, we observed that miRNAs are tailed to various extents, though generally not very high levels (Figure 3A, Figure S6A). Tailing was mostly mono-uridylation, with some miRNAs displaying significant adenylation or cytidylation, as previously observed (Figure 3A, Figure S6A) (Vieux et al, 2021). Overall tailing and miRNA abundance were not correlated, and the mir-35 family members were generally high in abundance, with a wide range of tailing frequencies observed across different members (Figure 3B, Table S4).…”

Section: Resultssupporting

confidence: 84%

“…We and others previously observed slight increases in the prevalence of tailed and trimmed miRNAs as miRNAs approach decay (Baccarini et al, 2011; Kingston and Bartel, 2019; Vieux et al, 2021). In TDMD, miRNAs often experience very high levels of tailing and/or trimming (generally ≥20-40% tailed or trimmed isoforms) (Ameres et al, 2010; Baccarini et al, 2011; Bitetti et al, 2018; Cazalla et al, 2010; Ghini et al, 2018; Kleaveland et al, 2018; Li et al, 2021; Marcinowski et al, 2012).…”

Section: Resultsmentioning

confidence: 60%

“…While much is known about the biogenesis and functions of miRNAs, relatively little is known about the mechanisms of decay of mature miRNAs. While half-lives of miRNAs vary, what determines these differences in stability is for the most part unknown (Bail et al, 2010; Kingston and Bartel, 2019; Lehrbach et al, 2012; Marzi et al, 2016; Miki et al, 2014; Reichholf et al, 2019; Vieux et al, 2021). Thus far, multiple phenomena regulating miRNA stability have been observed, with different degrees of sequence-specificity.…”

Section: Introductionmentioning

confidence: 99%

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The developmentally-timed decay of an essential microRNA family is seed sequence-dependent

Donnelly

Yang

Liu

et al. 2021

Preprint

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MicroRNA (miRNA) abundance is tightly controlled by regulation of biogenesis and decay. Here we show that the mir-35 miRNA family undergoes regulated decay at the transition from embryonic to larval development in C. elegans. The seed sequence of the miRNA is necessary and sufficient for this regulation. Sequences outside the seed (3’ end) regulate mir-35 abundance in the embryo but are not necessary for sharp decay at the transition to larval development. Enzymatic modifications of the miRNA 3’ end are neither prevalent nor correlated with changes in decay, suggesting that miRNA 3’ end display is not a core feature of this mechanism and further supporting a seed-driven decay model. Our findings demonstrate that seed sequence-specific decay can selectively and coherently regulate all redundant members of a miRNA seed family, a class of mechanism that has great biological and therapeutic potential for dynamic regulation of a miRNA family’s target repertoire.

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Section: Resultssupporting

confidence: 84%

Section: Resultsmentioning

confidence: 60%

Section: Introductionmentioning

confidence: 99%

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The developmentally-timed decay of an essential microRNA family is seed sequence-dependent

Donnelly

Yang

Liu

et al. 2021

Preprint

Self Cite

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“…By contrast, whether or not miRNA tailing determines miRNA stability remains debatable. Consistent with several recent studies 35,53,54 , we found that the loss of uridylation or adenylation did not coincide with changes in miRNA abundance at a global scale. This suggests that 3’ tailing does not play a general role in miRNA turnover.…”

Section: Discussionsupporting

confidence: 91%

TENT2, TUT4, and TUT7 selectively regulate miRNA sequence and abundance

Yang¹,

Ros²,

Stanton³

et al. 2022

Preprint

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TENTs generate miRNA isoforms by 3’ tailing. However, little is known about how tailing regulates miRNA function. Here, we generated isogenic HEK293T cell lines in which TENT2, TUT4 and TUT7 were knocked out individually or in combination. Together with rescue experiments, we characterized TENT-specific effects by deep sequencing, Northern blot and in vitro assays. We found that 3’ tailing is not random but highly specific. In addition to its known adenylation, TENT2 contributes to guanylation and uridylation on mature miRNAs. TUT4 uridylates most miRNAs whereas TUT7 is dispensable. Removing adenylation has a marginal impact on miRNA levels. By contrast, abolishing uridylation leads to dysregulation of a set of miRNAs. Besides let-7, miR-181b and miR-222 are negatively regulated by TUT4/7 via distinct mechanisms while the miR-888 cluster is upregulated specifically by TUT7. Our results uncover the selective actions of TENTs in generating 3’ isomiRs and pave the way to investigate their functions.

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“…These structural data raise the question of potential uncoupling between TDMD and tailing and trimming since the miRNA become available for modification in this conformation (discussed in Pawlica et al, 2019). Accordingly, other studies demonstrate that the tailing and trimming machineries are implicated in miRNA decay but not strictly required for TDMD (Yang et al, 2020) and that the disruption of tailing has no impact on miRNA turnover (Vieux et al, 2021).…”

Section: Risc Binding Outcomesmentioning

confidence: 99%

Regulation and different functions of the animal microRNA‐induced silencing complex

Frédérick

Simard

2021

WIREs RNA

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Among the different types of small RNAs, microRNAs (miRNAs) are key players in controlling gene expression at the mRNA level. To be active, they must associate with an Argonaute protein to form the miRNA induced silencing complex (miRISC) and binds to specific mRNA through complementarity sequences. The miRISC binding to an mRNA can lead to multiple outcomes, the most frequent being inhibition of the translation and/or deadenylation followed by decapping and mRNA decay. In the last years, several studies described different mechanisms modulating miRISC functions in animals. For instance, the regulation of the Argonaute protein through post-translational modifications can change the miRISC gene regulatory activity as well as modulate its binding to proteins, mRNA targets and miRISC stability. Furthermore, the presence of RNA binding proteins and multiple miRISCs at the targeted mRNA 3 0 untranslated region (3 0 UTR) can also affect its function through cooperation or competition mechanisms, underlying the importance of the 3 0 UTR environment in miRNA-mediated repression. Another way to regulate the miRISC function is by modulation of its interactors, forming different types of miRNA silencing complexes that affect gene regulation differently. It is also reported that the subcellular localization of several components of the miRNA pathway can modulate miRISC function, suggesting an important role for vesicular trafficking in the regulation of this essential silencing complex.

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Screening by deep sequencing reveals mediators of microRNA tailing inC. elegans

Cited by 6 publications

References 90 publications

The developmentally-timed decay of an essential microRNA family is seed sequence-dependent

The developmentally-timed decay of an essential microRNA family is seed sequence-dependent

TENT2, TUT4, and TUT7 selectively regulate miRNA sequence and abundance

Regulation and different functions of the animal microRNA‐induced silencing complex

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