Deadenylation by the <scp>CCR</scp>4‐<scp>NOT</scp> complex contributes to the turnover of <i>hairy</i>‐related <scp>mRNA</scp>s in the zebrafish segmentation clock

Fujino, Yuuri; Yamada, Kazuya; Sugaya, Chihiro; Ooka, Yuko; Ovara, Hiroki; Ban, Hiroyuki; Akama, Kagari; Otosaka, Shiori; Kinoshita, Hiroki; Yamasu, Kyo; Mishima, Yuichiro; Kawamura, Akinori

doi:10.1002/1873-3468.13261

Cited by 9 publications

(6 citation statements)

References 42 publications

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“…They clearly showed that the 3′UTR of the EC gene Lfng promoted rapid mRNA decay, while the 3′UTR of fgf8 mRNA contributed to stabilization of the reporter mRNA (Hilgers et al, 2005), which is compatible with fgf8 graded expression pattern in the PSM (Dubrulle and Pourquié, 2004). Similar findings were reported for zebrafish EC genes (Fujino et al, 2018), evidencing that 3′UTR-mediated regulation of EC gene expression oscillations is a conserved feature in vertebrates. The Amacher lab went on to specify that mRNA decay of both zebrafish her1 and deltaC relies on the Pumilio response-and AU-rich-elements present in their distal 3′UTRs, in a Pnrc2-dependent manner (Gallagher et al, 2017;Tietz et al, 2020).…”

Section: Mrna Degradation Delaysupporting

confidence: 86%

“…These authors measured the lengths of the poly(A) tails of zebrafish her1, her7 and hes6, and observed that the first two genes, that display cyclic expression in the PSM, have shorter poly(A) tails, while hes6 that is expressed in a gradient has a longer one. Through the inhibition of the deadenylase complex CCR4-NOT, the authors were able to lengthen the poly(A) tails of her1 and her7, and this resulted in a 2-3-fold increase in mRNA levels, indicating an increase in mRNA stability (Fujino et al, 2018).…”

Section: Mrna Degradation Delaymentioning

confidence: 99%

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The vertebrate Embryo Clock: Common players dancing to a different beat

Carraco

Martins-Jesus

Andrade

2022

Front. Cell Dev. Biol.

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Vertebrate embryo somitogenesis is the earliest morphological manifestation of the characteristic patterned structure of the adult axial skeleton. Pairs of somites flanking the neural tube are formed periodically during early development, and the molecular mechanisms in temporal control of this early patterning event have been thoroughly studied. The discovery of a molecular Embryo Clock (EC) underlying the periodicity of somite formation shed light on the importance of gene expression dynamics for pattern formation. The EC is now known to be present in all vertebrate organisms studied and this mechanism was also described in limb development and stem cell differentiation. An outstanding question, however, remains unanswered: what sets the different EC paces observed in different organisms and tissues? This review aims to summarize the available knowledge regarding the pace of the EC, its regulation and experimental manipulation and to expose new questions that might help shed light on what is still to unveil.

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Section: Mrna Degradation Delaysupporting

confidence: 86%

Section: Mrna Degradation Delaymentioning

confidence: 99%

The vertebrate Embryo Clock: Common players dancing to a different beat

Carraco

Martins-Jesus

Andrade

2022

Front. Cell Dev. Biol.

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“…Quantitative PCR analysis qPCR was carried out as essentially previously described (Fujino et al, 2018). Total RNA was extracted from wild-type, tbx6 ΔTR1/ΔTR1 and tbx6 −/− embryos at the 10-to 12-somite stage and subject to qPCR analysis.…”

Section: Luciferase Reporter Assaymentioning

confidence: 99%

Transcriptional autoregulation of zebrafish tbx6 is required for somite segmentation

et al. 2019

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The presumptive somite boundary in the presomitic mesoderm (PSM) is defined by the anterior border of the expression domain of Tbx6 protein. During somite segmentation, the expression domain of Tbx6 is regressed by Ripply-meditated degradation of Tbx6 protein. Although the expression of zebrafish tbx6 remains restricted to the PSM, the transcriptional regulation of tbx6 remains poorly understood. Here, we show that the expression of zebrafish tbx6 is maintained by transcriptional autoregulation. We find that a proximallocated cis-regulatory module, TR1, which contains two putative Tbox sites, is required for somite segmentation in the intermediate body and for proper expression of segmentation genes. Embryos with deletion of TR1 exhibit significant reduction of tbx6 expression at the 12-somite stage, although its expression is initially observed. Additionally, Tbx6 is associated with TR1 and activates its own expression in the anterior PSM. Furthermore, the anterior expansion of tbx6 expression in ripply gene mutants is suppressed in a TR1dependent manner. The results suggest that the autoregulatory loop of zebrafish tbx6 facilitates immediate removal of Tbx6 protein through termination of its own transcription at the anterior PSM.

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“…Short poly(A) tails are associated with mRNA degradation (44), and tim mRNA is thus likely unstable, as expected for a cycling transcript (14). Similarly, short half-life transcripts that encode transcription factors of the zebrafish segmentation clock display short poly(A) tails whose size is controlled by the CCR4-NOT1 complex (45). Short poly(A) tails have been recently associated with high translational efficiency (46) and the two effects of short poly(A) (instability and high translation) might be important for keeping high-amplitude tim mRNA oscillations.…”

Section: Discussionmentioning

confidence: 98%

PERIOD-controlled deadenylation of the timeless transcript in the Drosophila circadian clock

Grima

Papin

Martin

et al. 2019

Proc. Natl. Acad. Sci. U.S.A.

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The Drosophila circadian oscillator relies on a negative transcriptional feedback loop, in which the PERIOD (PER) and TIMELESS (TIM) proteins repress the expression of their own gene by inhibiting the activity of the CLOCK (CLK) and CYCLE (CYC) transcription factors. A series of posttranslational modifications contribute to the oscillations of the PER and TIM proteins but few posttranscriptional mechanisms have been described that affect mRNA stability. Here we report that down-regulation of the POP2 deadenylase, a key component of the CCR4-NOT deadenylation complex, alters behavioral rhythms. Downregulating POP2 specifically increases TIM protein and tim mRNA but not tim pre-mRNA, supporting a posttranscriptional role. Indeed, reduced POP2 levels induce a lengthening of tim mRNA poly(A) tail. Surprisingly, such effects are lost in per 0 mutants, supporting a PERdependent inhibition of tim mRNA deadenylation by POP2. We report a deadenylation mechanism that controls the oscillations of a core clock gene transcript. circadian rhythms | clock genes | mRNA poly(A) tail | CAF1/POP2 | CCR4-NOT complex

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Deadenylation by the CCR4‐NOT complex contributes to the turnover of hairy‐related mRNAs in the zebrafish segmentation clock

Cited by 9 publications

References 42 publications

The vertebrate Embryo Clock: Common players dancing to a different beat

The vertebrate Embryo Clock: Common players dancing to a different beat

Transcriptional autoregulation of zebrafish tbx6 is required for somite segmentation

PERIOD-controlled deadenylation of the timeless transcript in the Drosophila circadian clock

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